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Obesity and Cancer: Untangling a Complex Web
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
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This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco.</metaDescription> <articlePDF/> <teaserImage/> <teaser>Is gaining weight later in life better or worse for cancer risk than being overweight or obese from a young age?</teaser> <title>Obesity and Cancer: Untangling a Complex Web</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>fp</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>pn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>im</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>chph</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>skin</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>endo</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>nr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Neurology Reviews</journalTitle> <journalFullTitle>Neurology Reviews</journalFullTitle> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> <publicationData> <publicationCode>ob</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>hemn</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> <publicationData> <publicationCode>GIHOLD</publicationCode> <pubIssueName>January 2014</pubIssueName> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">31</term> <term>15</term> <term>25</term> <term>21</term> <term>6</term> <term>13</term> <term>34</term> <term>22</term> <term>23</term> <term>18</term> </publications> <sections> <term>39313</term> <term canonical="true">27980</term> </sections> <topics> <term canonical="true">280</term> <term>270</term> <term>31848</term> <term>292</term> <term>192</term> <term>198</term> <term>61821</term> <term>59244</term> <term>67020</term> <term>214</term> <term>217</term> <term>221</term> <term>238</term> <term>240</term> <term>242</term> <term>27442</term> <term>256</term> <term>245</term> <term>39570</term> <term>271</term> <term>206</term> <term>261</term> <term>263</term> <term>210</term> <term>178</term> <term>179</term> <term>181</term> <term>59374</term> <term>196</term> <term>197</term> <term>37637</term> <term>233</term> <term>243</term> <term>49434</term> <term>250</term> <term>303</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Obesity and Cancer: Untangling a Complex Web</title> <deck/> </itemMeta> <itemContent> <p>According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.</p> <p>The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. <br/><br/>Is obesity the new smoking? Not exactly.<br/><br/><span class="tag metaDescription">Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. </span>While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about <a href="https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21440">8% of incident cancers</a> are attributed to excess body weight. People often develop those diseases regardless of weight.<br/><br/>Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?<br/><br/>There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?<br/><br/>When it comes to weight and cancer risk, “there’s a lot we don’t know,” said <a href="https://cancercenter.arizona.edu/person/jennifer-w-bea-phd">Jennifer W. Bea,</a> PhD, associate professor, health promotion sciences, University of Arizona, Tucson.</p> <h2>A Consistent but Complicated Relationship</h2> <p>Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.</p> <p>Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.<br/><br/>“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said <a href="https://www.dana-farber.org/find-a-doctor/jeffrey-a-meyerhardt">Jeffrey A. Meyerhardt,</a> MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.<br/><br/>In a widely cited <span class="Hyperlink"><a href="https://www.nejm.org/doi/10.1056/NEJMsr1606602?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov">report</a></span> published in <em>The New England Journal of Medicine</em> in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.<br/><br/>That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.<br/><br/>At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. <br/><br/>It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.<br/><br/>Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said <a href="https://faculty.mdanderson.org/profiles/karen_basen-engquist.html">Karen M. Basen-Engquist,</a> PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.<br/><br/>One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. <br/><br/>But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.<br/><br/>That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.</p> <h2>How Big Is the Effect?</h2> <p>While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. </p> <p>Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.<br/><br/>With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.<br/><br/>A 2018 <a href="https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21440">study</a> from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).<br/><br/>Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.<br/><br/>Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.<br/><br/><a href="https://www.cdc.gov/pcd/issues/2023/22_0211.htm">CDC data</a> show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.<br/><br/>Obesity may be one reason for growing cancer disparities, said <a href="https://ysph.yale.edu/profile/leah-ferrucci/">Leah Ferrucci,</a> PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.</p> <h2>When Do Extra Pounds Matter?</h2> <p>When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?</p> <p>Some evidence suggests there’s no “safe” time for putting on excess pounds.<br/><br/>A recent <a href="https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-024-01804-x">meta-analysis</a> concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2804676">study</a> in <em>JAMA Network Open</em> found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. <br/><br/>The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.<br/><br/>Those studies focused on later-onset disease. But, in recent years, experts have tracked a <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808381">troubling rise</a> in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. <br/><br/>An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.<br/><br/>There’s some data to support that, he said. An <a href="https://jamanetwork.com/journals/jamaoncology/fullarticle/2705608">analysis</a> from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.<br/><br/>But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.<br/><br/>“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”</p> <h2>Does Weight Loss Help?</h2> <p>With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.</p> <p>Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A <span class="Hyperlink"><a href="https://jamanetwork.com/journals/jama/fullarticle/2793220">study</a></span> published in <em>JAMA</em> found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.<br/><br/>Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. <br/><br/>A 2020 <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492760/">pooled analysis</a> found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.<br/><br/>But other research <a href="https://www.medscape.com/viewarticle/999788">suggests the opposite</a>. A <a href="https://jamanetwork.com/journals/jama/article-abstract/2814132">recent analysis</a> found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.<br/><br/>Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”<br/><br/>“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”<br/><br/>Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. <br/><br/>People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to <a href="https://www.cancer.org/cancer/risk-prevention/diet-physical-activity/acs-guidelines-nutrition-physical-activity-cancer-prevention/guidelines.html">exercising several hours a week</a>. <br/><br/>“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/obesity-and-cancer-untangling-complex-web-2024a10009zi">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
Does Exercise Reduce Cancer Risk? It’s Just Not That Simple
“Exercise is medicine” has become something of a mantra, with good reason. There’s no doubt that regular physical activity has a broad range of health benefits. Exercise can improve circulation, help control weight, reduce stress, and boost mood — take your pick.
Lower cancer risk is also on the list — with exercise promoted as a risk-cutting strategy in government guidelines and in recommendations from professional groups such as the American Cancer Society.
The bulk of the data hangs on less rigorous, observational studies that have linked physical activity to lower risks for certain cancers, but plenty of questions remain.
What are the cancer types where exercise makes a difference? How significant is that impact? And what, exactly, defines a physical activity pattern powerful enough to move the needle on cancer risk?
Here’s an overview of the state of the evidence.
Exercise and Cancer Types: A Mixed Bag
When it comes to cancer prevention strategies, guidelines uniformly endorse less couch time and more movement. But a deeper look at the science reveals a complex and often poorly understood connection between exercise and cancer risk.
For certain cancer types, the benefits of exercise on cancer risk seem fairly well established.
The latest edition of the Physical Activity Guidelines for Americans, published in 2018, cites “strong evidence” that regular exercise might curb the risks for breast and colon cancers as well as bladder, endometrial, esophageal, kidney, and gastric cancers. These guidelines also point to “moderate”-strength evidence of a protective association with lung cancer.
The evidence of a protective effect, however, is strongest for breast and colon cancers, said Jennifer Ligibel, MD, senior physician in the Breast Oncology Center at Dana-Farber Cancer Institute, Boston, . “But,” she pointed out, “that may be because they’re some of the most common cancers, and it’s been easier to detect an association.”
Guidelines from the American Cancer Society, published in 2020, align with the 2018 recommendations.
“We believe there’s strong evidence to suggest at least eight different types of cancer are associated with physical activity,” said Erika Rees-Punia, PhD, MPH, senior principal scientist, epidemiology and behavioral research at the American Cancer Society.
That view is not universal, however. Current recommendations from the World Cancer Research Fund and American Institute for Cancer Research, for example, are more circumspect, citing only three cancers with good evidence of a protective effect from exercise: Breast (postmenopausal), colon, and endometrial.
“We definitely can’t say exercise reduces the risk of all cancers,” said Lee Jones, PhD, head of the Exercise Oncology Program at Memorial Sloan Kettering Cancer Center in New York City. “The data suggest it’s just not that simple.”
And it’s challenging to put all the evidence together, Dr. Jones added.
The physical activity guidelines are based on published systematic reviews, meta-analyses, and pooled analyses of data from observational studies that examined the relationship between physical activity — aerobic exercise, specifically — and cancer incidence. That means the evidence comes with all the limitations observational studies entail, such as how they collect information on participants’ exercise habits — which, Dr. Jones noted, is typically done via “monster questionnaires” that gauge physical activity in broad strokes.
Pooling all those findings into a meta-analysis is tricky, Dr. Jones added, because individual studies vary in important ways — from follow-up periods to how they quantify exercise and track cancer incidence.
In a study published in February in Cancer Cell, Dr. Jones and his colleagues attempted to address some of those issues by leveraging data from the PLCO screening trial.
The PLCO was a prospective study of over 60,000 US adults that compared the effects of annual screening vs usual care on cancer mortality. At enrollment, participants completed questionnaires that included an assessment of “vigorous” exercise. Based on that, Dr. Jones and his colleagues classified 55% as “exercisers” — meaning they reported 2 or more hours of vigorous exercise per week. The remaining 45%, who were in the 0 to 1 hour per week range, were deemed non-exercisers.
Over a median of 18 years, nearly 16,000 first-time invasive cancers were diagnosed, and some interesting differences between exercisers and non-exercisers emerged. The active group had lower risks for three cancers: Head and neck, with a 26% lower risk (hazard ratio [HR], 0.74), lung (a 20% lower risk), and breast (an 11% lower risk).
What was striking, however, was the lack of connection between exercise and many cancers cited in the guidelines, including colon, gastric, bladder, endometrial, and renal cancers.
Perhaps even more surprising — exercisers had higher risks for prostate cancer (12%) and melanoma (20%). This finding, Dr. Jones said, is in line with a previous pooled analysis of data from 12 US and European prospective cohorts. In this study, the most physically active participants (90th percentile) had higher risks for melanoma and prostate cancer, compared with the least active group (10th percentile).
The melanoma findings do make sense, Dr. Jones said, given that highly active people may spend a lot of time in the sun. “My advice,” Dr. Jones said, “is, if you’re exercising outside, wear sunscreen.” The prostate cancer findings, however, are more puzzling and warrant further research, he noted.
But the bottom line is that the relationship between exercise and cancer types is mixed and far from nailed down.
How Big Is the Effect?
Even if exercise reduces the risk for only certain cancers, that’s still important, particularly when those links appear strongest for common cancer types, such as breast and colon.
But how much of a difference can exercise make?
Based on the evidence, it may only be a modest one. A 2019 systematic review by the Physical Activity Guidelines Advisory Committee provided a rough estimate: Across hundreds of epidemiological studies, people with the highest physical activity levels had a 10%-20% lower risk for the cancers cited in the 2018 exercise guidelines compared with people who were least active.
These figures, however, are probably an underestimate, said Anne McTiernan, MD, PhD, a member of the advisory committee and professor of epidemiology, at Fred Hutchinson Cancer Center, Seattle.
“This is what we usually see when a factor is not measured very well,” said Dr. McTiernan, explaining that the individual studies differed in their categories of “highest” and “lowest” physical activity, such that one study’s “highest” could be another’s mid-range.
“In other words, the effects of physical activity are likely larger” than the review found, Dr. McTiernan said.
The next logical question is whether a bigger exercise “dose” — more time or higher intensity — would have a greater impact on cancer risk. A 2019 study published in the Journal of Clinical Oncology tried to clarify that by pooling data on over 750,000 participants from nine prospective cohorts.
Overall, people meeting government recommendations for exercise — equivalent to about 2.5-5 hours of weekly moderate activity, such as a brisk walk, or about 1.25-2.5 hours of more vigorous activities, like running — had lower risks for seven of 15 cancer types studied compared with less active people.
For cancers with positive findings, being on the higher end of the recommended 2.5- to 5-hour weekly range was better. Risk reductions for breast cancer, for instance, were 6% at 2.5 hours of physical activity per week and 10% at 5 hours per week. Similar trends emerged for other cancer types, including colon (8%-14%), endometrial (10%-18%), liver cancer (18%-27%), and non-Hodgkin lymphoma in women (11%-18%).
But there may be an exercise sweet spot that maximizes the cancer risk benefit.
Among people who surpassed the recommendations — exercising for more time or more intensely — the risk reduction benefit did not necessarily improve in a linear fashion. For certain cancer types, such as colon and endometrial, the benefits of more vigorous exercise “eroded at higher levels of activity,” the authors said.
The issue here is that most studies have not dug deeply into aerobic exercise habits. Often, studies present participants with a list of activities — walking, biking, and running — and ask them to estimate how often and for what duration they do each.
Plus, “we’ve usually lumped moderate and vigorous activities together,” Dr. Rees-Punia said, which means there’s a lack of “granular data” to say whether certain intensities or frequencies of exercise are optimal and for whom.
Why Exercise May Lower Cancer Risk
Exercise habits do not, of course, exist in a vacuum. Highly active people, Dr. Ligibel said, tend to be of higher socioeconomic status, leaner, and have generally healthier lifestyles than sedentary people.
Body weight is a big confounder as well. However, Dr. Rees-Punia noted, it’s also probably a reason that exercise is linked to lower cancer risks, particularly by preventing weight gain. Still, studies have found that the association between exercise and many cancers remains significant after adjusting for body mass index.
The why remains unclear, though some studies offer clues.
“There’s been some really interesting mechanistic research, suggesting that exercise may help inhibit tumor growth or upregulate the immune system,” Dr. Ligibel said.
That includes not only lab research but small intervention studies. While these studies have largely involved people who already have cancer, some have also focused on healthy individuals.
A 2019 study from Dr. Ligibel and her colleagues, which randomly assigned 49 women newly diagnosed with breast cancer to start either an exercise program or mind-body practices ahead of surgery, found exercisers, who had been active for about a month at the time of surgery, showed signs of immune system upregulation in their tumors, while the control group did not.
Among healthy postmenopausal women, a meta-analysis of six clinical trials from Dr. McTiernan and her colleagues found that exercise plus calorie reduction can reduce levels of breast cancer-related endogenous hormones, more so than calorie-cutting alone. And a 2023 study found that high-intensity exercise boosted the ranks of certain immune cells and reduced inflammation in the colon among people at high risk for colon and endometrial cancers due to Lynch syndrome.
Defining an Exercise ‘Prescription’
Despite the gaps and uncertainties in the research, government guidelines as well as those from the American Cancer Society and other medical groups are in lockstep in their exercise recommendations: Adults should strive for 150-300 minutes of moderate-intensity aerobic exercise (like brisk walking), 75-150 minutes of vigorous activity (like running), or some combination each week.
The guidelines also encourage strength training twice a week — advice that’s based on research tying those activity levels to lower risks for heart disease, diabetes, and other chronic conditions.
But there’s no “best” exercise prescription for lowering cancer risk specifically. Most epidemiological studies have examined only aerobic activity, Dr. Rees-Punia said, and there’s very little known about whether strength conditioning or other moderate heart rate-elevating activities, such as daily household chores, may reduce the risk for cancer.
Given the lack of nuance in the literature, it’s hard to say what intensities, types, or amounts of exercise are best for each individual.
Going forward, device-based measurements of physical activity could “help us sort out the effects of different intensities of exercise and possibly types,” Dr. Rees-Punia said.
But overall, Dr. McTiernan said, the data do show that the risks for several cancers are lower at the widely recommended activity levels.
“The bottom-line advice is still to exercise at least 150 minutes per week at a moderate-intensity level or greater,” Dr. McTiernan said.
Or put another way, moving beats being sedentary. It’s probably wise for everyone to sit less, noted Dr. Rees-Punia, for overall health and based on evidence tying sedentary time to the risks for certain cancers, including colon, endometrial, and lung.
There’s a practical element to consider in all of this: What physical activities will people actually do on the regular? In the big epidemiological studies, Dr. McTiernan noted, middle-aged and older adults most often report walking, suggesting that’s the preferred, or most accessible activity, for many.
“You can only benefit from the physical activity you’ll actually do,” Dr. Rees-Punia said.
Dr. Ligibel echoed that sentiment, saying she encourages patients to think about physical activity as a process: “You need to find things you like to do and work them into your daily life, in a sustainable way.
“People often talk about exercise being medicine,” Dr. Ligibel said. “But I think you could take that too far. If we get too prescriptive about it, that could take the joy away.”
A version of this article appeared on Medscape.com.
“Exercise is medicine” has become something of a mantra, with good reason. There’s no doubt that regular physical activity has a broad range of health benefits. Exercise can improve circulation, help control weight, reduce stress, and boost mood — take your pick.
Lower cancer risk is also on the list — with exercise promoted as a risk-cutting strategy in government guidelines and in recommendations from professional groups such as the American Cancer Society.
The bulk of the data hangs on less rigorous, observational studies that have linked physical activity to lower risks for certain cancers, but plenty of questions remain.
What are the cancer types where exercise makes a difference? How significant is that impact? And what, exactly, defines a physical activity pattern powerful enough to move the needle on cancer risk?
Here’s an overview of the state of the evidence.
Exercise and Cancer Types: A Mixed Bag
When it comes to cancer prevention strategies, guidelines uniformly endorse less couch time and more movement. But a deeper look at the science reveals a complex and often poorly understood connection between exercise and cancer risk.
For certain cancer types, the benefits of exercise on cancer risk seem fairly well established.
The latest edition of the Physical Activity Guidelines for Americans, published in 2018, cites “strong evidence” that regular exercise might curb the risks for breast and colon cancers as well as bladder, endometrial, esophageal, kidney, and gastric cancers. These guidelines also point to “moderate”-strength evidence of a protective association with lung cancer.
The evidence of a protective effect, however, is strongest for breast and colon cancers, said Jennifer Ligibel, MD, senior physician in the Breast Oncology Center at Dana-Farber Cancer Institute, Boston, . “But,” she pointed out, “that may be because they’re some of the most common cancers, and it’s been easier to detect an association.”
Guidelines from the American Cancer Society, published in 2020, align with the 2018 recommendations.
“We believe there’s strong evidence to suggest at least eight different types of cancer are associated with physical activity,” said Erika Rees-Punia, PhD, MPH, senior principal scientist, epidemiology and behavioral research at the American Cancer Society.
That view is not universal, however. Current recommendations from the World Cancer Research Fund and American Institute for Cancer Research, for example, are more circumspect, citing only three cancers with good evidence of a protective effect from exercise: Breast (postmenopausal), colon, and endometrial.
“We definitely can’t say exercise reduces the risk of all cancers,” said Lee Jones, PhD, head of the Exercise Oncology Program at Memorial Sloan Kettering Cancer Center in New York City. “The data suggest it’s just not that simple.”
And it’s challenging to put all the evidence together, Dr. Jones added.
The physical activity guidelines are based on published systematic reviews, meta-analyses, and pooled analyses of data from observational studies that examined the relationship between physical activity — aerobic exercise, specifically — and cancer incidence. That means the evidence comes with all the limitations observational studies entail, such as how they collect information on participants’ exercise habits — which, Dr. Jones noted, is typically done via “monster questionnaires” that gauge physical activity in broad strokes.
Pooling all those findings into a meta-analysis is tricky, Dr. Jones added, because individual studies vary in important ways — from follow-up periods to how they quantify exercise and track cancer incidence.
In a study published in February in Cancer Cell, Dr. Jones and his colleagues attempted to address some of those issues by leveraging data from the PLCO screening trial.
The PLCO was a prospective study of over 60,000 US adults that compared the effects of annual screening vs usual care on cancer mortality. At enrollment, participants completed questionnaires that included an assessment of “vigorous” exercise. Based on that, Dr. Jones and his colleagues classified 55% as “exercisers” — meaning they reported 2 or more hours of vigorous exercise per week. The remaining 45%, who were in the 0 to 1 hour per week range, were deemed non-exercisers.
Over a median of 18 years, nearly 16,000 first-time invasive cancers were diagnosed, and some interesting differences between exercisers and non-exercisers emerged. The active group had lower risks for three cancers: Head and neck, with a 26% lower risk (hazard ratio [HR], 0.74), lung (a 20% lower risk), and breast (an 11% lower risk).
What was striking, however, was the lack of connection between exercise and many cancers cited in the guidelines, including colon, gastric, bladder, endometrial, and renal cancers.
Perhaps even more surprising — exercisers had higher risks for prostate cancer (12%) and melanoma (20%). This finding, Dr. Jones said, is in line with a previous pooled analysis of data from 12 US and European prospective cohorts. In this study, the most physically active participants (90th percentile) had higher risks for melanoma and prostate cancer, compared with the least active group (10th percentile).
The melanoma findings do make sense, Dr. Jones said, given that highly active people may spend a lot of time in the sun. “My advice,” Dr. Jones said, “is, if you’re exercising outside, wear sunscreen.” The prostate cancer findings, however, are more puzzling and warrant further research, he noted.
But the bottom line is that the relationship between exercise and cancer types is mixed and far from nailed down.
How Big Is the Effect?
Even if exercise reduces the risk for only certain cancers, that’s still important, particularly when those links appear strongest for common cancer types, such as breast and colon.
But how much of a difference can exercise make?
Based on the evidence, it may only be a modest one. A 2019 systematic review by the Physical Activity Guidelines Advisory Committee provided a rough estimate: Across hundreds of epidemiological studies, people with the highest physical activity levels had a 10%-20% lower risk for the cancers cited in the 2018 exercise guidelines compared with people who were least active.
These figures, however, are probably an underestimate, said Anne McTiernan, MD, PhD, a member of the advisory committee and professor of epidemiology, at Fred Hutchinson Cancer Center, Seattle.
“This is what we usually see when a factor is not measured very well,” said Dr. McTiernan, explaining that the individual studies differed in their categories of “highest” and “lowest” physical activity, such that one study’s “highest” could be another’s mid-range.
“In other words, the effects of physical activity are likely larger” than the review found, Dr. McTiernan said.
The next logical question is whether a bigger exercise “dose” — more time or higher intensity — would have a greater impact on cancer risk. A 2019 study published in the Journal of Clinical Oncology tried to clarify that by pooling data on over 750,000 participants from nine prospective cohorts.
Overall, people meeting government recommendations for exercise — equivalent to about 2.5-5 hours of weekly moderate activity, such as a brisk walk, or about 1.25-2.5 hours of more vigorous activities, like running — had lower risks for seven of 15 cancer types studied compared with less active people.
For cancers with positive findings, being on the higher end of the recommended 2.5- to 5-hour weekly range was better. Risk reductions for breast cancer, for instance, were 6% at 2.5 hours of physical activity per week and 10% at 5 hours per week. Similar trends emerged for other cancer types, including colon (8%-14%), endometrial (10%-18%), liver cancer (18%-27%), and non-Hodgkin lymphoma in women (11%-18%).
But there may be an exercise sweet spot that maximizes the cancer risk benefit.
Among people who surpassed the recommendations — exercising for more time or more intensely — the risk reduction benefit did not necessarily improve in a linear fashion. For certain cancer types, such as colon and endometrial, the benefits of more vigorous exercise “eroded at higher levels of activity,” the authors said.
The issue here is that most studies have not dug deeply into aerobic exercise habits. Often, studies present participants with a list of activities — walking, biking, and running — and ask them to estimate how often and for what duration they do each.
Plus, “we’ve usually lumped moderate and vigorous activities together,” Dr. Rees-Punia said, which means there’s a lack of “granular data” to say whether certain intensities or frequencies of exercise are optimal and for whom.
Why Exercise May Lower Cancer Risk
Exercise habits do not, of course, exist in a vacuum. Highly active people, Dr. Ligibel said, tend to be of higher socioeconomic status, leaner, and have generally healthier lifestyles than sedentary people.
Body weight is a big confounder as well. However, Dr. Rees-Punia noted, it’s also probably a reason that exercise is linked to lower cancer risks, particularly by preventing weight gain. Still, studies have found that the association between exercise and many cancers remains significant after adjusting for body mass index.
The why remains unclear, though some studies offer clues.
“There’s been some really interesting mechanistic research, suggesting that exercise may help inhibit tumor growth or upregulate the immune system,” Dr. Ligibel said.
That includes not only lab research but small intervention studies. While these studies have largely involved people who already have cancer, some have also focused on healthy individuals.
A 2019 study from Dr. Ligibel and her colleagues, which randomly assigned 49 women newly diagnosed with breast cancer to start either an exercise program or mind-body practices ahead of surgery, found exercisers, who had been active for about a month at the time of surgery, showed signs of immune system upregulation in their tumors, while the control group did not.
Among healthy postmenopausal women, a meta-analysis of six clinical trials from Dr. McTiernan and her colleagues found that exercise plus calorie reduction can reduce levels of breast cancer-related endogenous hormones, more so than calorie-cutting alone. And a 2023 study found that high-intensity exercise boosted the ranks of certain immune cells and reduced inflammation in the colon among people at high risk for colon and endometrial cancers due to Lynch syndrome.
Defining an Exercise ‘Prescription’
Despite the gaps and uncertainties in the research, government guidelines as well as those from the American Cancer Society and other medical groups are in lockstep in their exercise recommendations: Adults should strive for 150-300 minutes of moderate-intensity aerobic exercise (like brisk walking), 75-150 minutes of vigorous activity (like running), or some combination each week.
The guidelines also encourage strength training twice a week — advice that’s based on research tying those activity levels to lower risks for heart disease, diabetes, and other chronic conditions.
But there’s no “best” exercise prescription for lowering cancer risk specifically. Most epidemiological studies have examined only aerobic activity, Dr. Rees-Punia said, and there’s very little known about whether strength conditioning or other moderate heart rate-elevating activities, such as daily household chores, may reduce the risk for cancer.
Given the lack of nuance in the literature, it’s hard to say what intensities, types, or amounts of exercise are best for each individual.
Going forward, device-based measurements of physical activity could “help us sort out the effects of different intensities of exercise and possibly types,” Dr. Rees-Punia said.
But overall, Dr. McTiernan said, the data do show that the risks for several cancers are lower at the widely recommended activity levels.
“The bottom-line advice is still to exercise at least 150 minutes per week at a moderate-intensity level or greater,” Dr. McTiernan said.
Or put another way, moving beats being sedentary. It’s probably wise for everyone to sit less, noted Dr. Rees-Punia, for overall health and based on evidence tying sedentary time to the risks for certain cancers, including colon, endometrial, and lung.
There’s a practical element to consider in all of this: What physical activities will people actually do on the regular? In the big epidemiological studies, Dr. McTiernan noted, middle-aged and older adults most often report walking, suggesting that’s the preferred, or most accessible activity, for many.
“You can only benefit from the physical activity you’ll actually do,” Dr. Rees-Punia said.
Dr. Ligibel echoed that sentiment, saying she encourages patients to think about physical activity as a process: “You need to find things you like to do and work them into your daily life, in a sustainable way.
“People often talk about exercise being medicine,” Dr. Ligibel said. “But I think you could take that too far. If we get too prescriptive about it, that could take the joy away.”
A version of this article appeared on Medscape.com.
“Exercise is medicine” has become something of a mantra, with good reason. There’s no doubt that regular physical activity has a broad range of health benefits. Exercise can improve circulation, help control weight, reduce stress, and boost mood — take your pick.
Lower cancer risk is also on the list — with exercise promoted as a risk-cutting strategy in government guidelines and in recommendations from professional groups such as the American Cancer Society.
The bulk of the data hangs on less rigorous, observational studies that have linked physical activity to lower risks for certain cancers, but plenty of questions remain.
What are the cancer types where exercise makes a difference? How significant is that impact? And what, exactly, defines a physical activity pattern powerful enough to move the needle on cancer risk?
Here’s an overview of the state of the evidence.
Exercise and Cancer Types: A Mixed Bag
When it comes to cancer prevention strategies, guidelines uniformly endorse less couch time and more movement. But a deeper look at the science reveals a complex and often poorly understood connection between exercise and cancer risk.
For certain cancer types, the benefits of exercise on cancer risk seem fairly well established.
The latest edition of the Physical Activity Guidelines for Americans, published in 2018, cites “strong evidence” that regular exercise might curb the risks for breast and colon cancers as well as bladder, endometrial, esophageal, kidney, and gastric cancers. These guidelines also point to “moderate”-strength evidence of a protective association with lung cancer.
The evidence of a protective effect, however, is strongest for breast and colon cancers, said Jennifer Ligibel, MD, senior physician in the Breast Oncology Center at Dana-Farber Cancer Institute, Boston, . “But,” she pointed out, “that may be because they’re some of the most common cancers, and it’s been easier to detect an association.”
Guidelines from the American Cancer Society, published in 2020, align with the 2018 recommendations.
“We believe there’s strong evidence to suggest at least eight different types of cancer are associated with physical activity,” said Erika Rees-Punia, PhD, MPH, senior principal scientist, epidemiology and behavioral research at the American Cancer Society.
That view is not universal, however. Current recommendations from the World Cancer Research Fund and American Institute for Cancer Research, for example, are more circumspect, citing only three cancers with good evidence of a protective effect from exercise: Breast (postmenopausal), colon, and endometrial.
“We definitely can’t say exercise reduces the risk of all cancers,” said Lee Jones, PhD, head of the Exercise Oncology Program at Memorial Sloan Kettering Cancer Center in New York City. “The data suggest it’s just not that simple.”
And it’s challenging to put all the evidence together, Dr. Jones added.
The physical activity guidelines are based on published systematic reviews, meta-analyses, and pooled analyses of data from observational studies that examined the relationship between physical activity — aerobic exercise, specifically — and cancer incidence. That means the evidence comes with all the limitations observational studies entail, such as how they collect information on participants’ exercise habits — which, Dr. Jones noted, is typically done via “monster questionnaires” that gauge physical activity in broad strokes.
Pooling all those findings into a meta-analysis is tricky, Dr. Jones added, because individual studies vary in important ways — from follow-up periods to how they quantify exercise and track cancer incidence.
In a study published in February in Cancer Cell, Dr. Jones and his colleagues attempted to address some of those issues by leveraging data from the PLCO screening trial.
The PLCO was a prospective study of over 60,000 US adults that compared the effects of annual screening vs usual care on cancer mortality. At enrollment, participants completed questionnaires that included an assessment of “vigorous” exercise. Based on that, Dr. Jones and his colleagues classified 55% as “exercisers” — meaning they reported 2 or more hours of vigorous exercise per week. The remaining 45%, who were in the 0 to 1 hour per week range, were deemed non-exercisers.
Over a median of 18 years, nearly 16,000 first-time invasive cancers were diagnosed, and some interesting differences between exercisers and non-exercisers emerged. The active group had lower risks for three cancers: Head and neck, with a 26% lower risk (hazard ratio [HR], 0.74), lung (a 20% lower risk), and breast (an 11% lower risk).
What was striking, however, was the lack of connection between exercise and many cancers cited in the guidelines, including colon, gastric, bladder, endometrial, and renal cancers.
Perhaps even more surprising — exercisers had higher risks for prostate cancer (12%) and melanoma (20%). This finding, Dr. Jones said, is in line with a previous pooled analysis of data from 12 US and European prospective cohorts. In this study, the most physically active participants (90th percentile) had higher risks for melanoma and prostate cancer, compared with the least active group (10th percentile).
The melanoma findings do make sense, Dr. Jones said, given that highly active people may spend a lot of time in the sun. “My advice,” Dr. Jones said, “is, if you’re exercising outside, wear sunscreen.” The prostate cancer findings, however, are more puzzling and warrant further research, he noted.
But the bottom line is that the relationship between exercise and cancer types is mixed and far from nailed down.
How Big Is the Effect?
Even if exercise reduces the risk for only certain cancers, that’s still important, particularly when those links appear strongest for common cancer types, such as breast and colon.
But how much of a difference can exercise make?
Based on the evidence, it may only be a modest one. A 2019 systematic review by the Physical Activity Guidelines Advisory Committee provided a rough estimate: Across hundreds of epidemiological studies, people with the highest physical activity levels had a 10%-20% lower risk for the cancers cited in the 2018 exercise guidelines compared with people who were least active.
These figures, however, are probably an underestimate, said Anne McTiernan, MD, PhD, a member of the advisory committee and professor of epidemiology, at Fred Hutchinson Cancer Center, Seattle.
“This is what we usually see when a factor is not measured very well,” said Dr. McTiernan, explaining that the individual studies differed in their categories of “highest” and “lowest” physical activity, such that one study’s “highest” could be another’s mid-range.
“In other words, the effects of physical activity are likely larger” than the review found, Dr. McTiernan said.
The next logical question is whether a bigger exercise “dose” — more time or higher intensity — would have a greater impact on cancer risk. A 2019 study published in the Journal of Clinical Oncology tried to clarify that by pooling data on over 750,000 participants from nine prospective cohorts.
Overall, people meeting government recommendations for exercise — equivalent to about 2.5-5 hours of weekly moderate activity, such as a brisk walk, or about 1.25-2.5 hours of more vigorous activities, like running — had lower risks for seven of 15 cancer types studied compared with less active people.
For cancers with positive findings, being on the higher end of the recommended 2.5- to 5-hour weekly range was better. Risk reductions for breast cancer, for instance, were 6% at 2.5 hours of physical activity per week and 10% at 5 hours per week. Similar trends emerged for other cancer types, including colon (8%-14%), endometrial (10%-18%), liver cancer (18%-27%), and non-Hodgkin lymphoma in women (11%-18%).
But there may be an exercise sweet spot that maximizes the cancer risk benefit.
Among people who surpassed the recommendations — exercising for more time or more intensely — the risk reduction benefit did not necessarily improve in a linear fashion. For certain cancer types, such as colon and endometrial, the benefits of more vigorous exercise “eroded at higher levels of activity,” the authors said.
The issue here is that most studies have not dug deeply into aerobic exercise habits. Often, studies present participants with a list of activities — walking, biking, and running — and ask them to estimate how often and for what duration they do each.
Plus, “we’ve usually lumped moderate and vigorous activities together,” Dr. Rees-Punia said, which means there’s a lack of “granular data” to say whether certain intensities or frequencies of exercise are optimal and for whom.
Why Exercise May Lower Cancer Risk
Exercise habits do not, of course, exist in a vacuum. Highly active people, Dr. Ligibel said, tend to be of higher socioeconomic status, leaner, and have generally healthier lifestyles than sedentary people.
Body weight is a big confounder as well. However, Dr. Rees-Punia noted, it’s also probably a reason that exercise is linked to lower cancer risks, particularly by preventing weight gain. Still, studies have found that the association between exercise and many cancers remains significant after adjusting for body mass index.
The why remains unclear, though some studies offer clues.
“There’s been some really interesting mechanistic research, suggesting that exercise may help inhibit tumor growth or upregulate the immune system,” Dr. Ligibel said.
That includes not only lab research but small intervention studies. While these studies have largely involved people who already have cancer, some have also focused on healthy individuals.
A 2019 study from Dr. Ligibel and her colleagues, which randomly assigned 49 women newly diagnosed with breast cancer to start either an exercise program or mind-body practices ahead of surgery, found exercisers, who had been active for about a month at the time of surgery, showed signs of immune system upregulation in their tumors, while the control group did not.
Among healthy postmenopausal women, a meta-analysis of six clinical trials from Dr. McTiernan and her colleagues found that exercise plus calorie reduction can reduce levels of breast cancer-related endogenous hormones, more so than calorie-cutting alone. And a 2023 study found that high-intensity exercise boosted the ranks of certain immune cells and reduced inflammation in the colon among people at high risk for colon and endometrial cancers due to Lynch syndrome.
Defining an Exercise ‘Prescription’
Despite the gaps and uncertainties in the research, government guidelines as well as those from the American Cancer Society and other medical groups are in lockstep in their exercise recommendations: Adults should strive for 150-300 minutes of moderate-intensity aerobic exercise (like brisk walking), 75-150 minutes of vigorous activity (like running), or some combination each week.
The guidelines also encourage strength training twice a week — advice that’s based on research tying those activity levels to lower risks for heart disease, diabetes, and other chronic conditions.
But there’s no “best” exercise prescription for lowering cancer risk specifically. Most epidemiological studies have examined only aerobic activity, Dr. Rees-Punia said, and there’s very little known about whether strength conditioning or other moderate heart rate-elevating activities, such as daily household chores, may reduce the risk for cancer.
Given the lack of nuance in the literature, it’s hard to say what intensities, types, or amounts of exercise are best for each individual.
Going forward, device-based measurements of physical activity could “help us sort out the effects of different intensities of exercise and possibly types,” Dr. Rees-Punia said.
But overall, Dr. McTiernan said, the data do show that the risks for several cancers are lower at the widely recommended activity levels.
“The bottom-line advice is still to exercise at least 150 minutes per week at a moderate-intensity level or greater,” Dr. McTiernan said.
Or put another way, moving beats being sedentary. It’s probably wise for everyone to sit less, noted Dr. Rees-Punia, for overall health and based on evidence tying sedentary time to the risks for certain cancers, including colon, endometrial, and lung.
There’s a practical element to consider in all of this: What physical activities will people actually do on the regular? In the big epidemiological studies, Dr. McTiernan noted, middle-aged and older adults most often report walking, suggesting that’s the preferred, or most accessible activity, for many.
“You can only benefit from the physical activity you’ll actually do,” Dr. Rees-Punia said.
Dr. Ligibel echoed that sentiment, saying she encourages patients to think about physical activity as a process: “You need to find things you like to do and work them into your daily life, in a sustainable way.
“People often talk about exercise being medicine,” Dr. Ligibel said. “But I think you could take that too far. If we get too prescriptive about it, that could take the joy away.”
A version of this article appeared on Medscape.com.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>Despite confidently worded recommendations, the relationship between exercise and cancer risk is much less certain than the guidelines would suggest.</metaDescription> <articlePDF/> <teaserImage/> <teaser>What are the cancer types where exercise makes a difference? </teaser> <title>Does Exercise Reduce Cancer Risk? 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It’s Just Not That Simple</title> <deck/> </itemMeta> <itemContent> <p>“Exercise is medicine” has become something of a mantra, with good reason. There’s no doubt that regular physical activity has a broad range of health benefits. Exercise can improve circulation, help control weight, reduce stress, and boost mood — take your pick.</p> <p>Lower cancer risk is also on the list — with exercise promoted as a risk-cutting strategy in government guidelines and in recommendations from professional groups such as <a href="https://www.cancer.org/cancer/risk-prevention/diet-physical-activity/acs-guidelines-nutrition-physical-activity-cancer-prevention/guidelines.html">the American Cancer Society</a>.<br/><br/><span class="tag metaDescription">Despite confidently worded recommendations, the relationship between exercise and cancer risk is much less certain than the guidelines would suggest. </span>The bulk of the data hangs on less rigorous, observational studies that have linked physical activity to lower risks for certain cancers, but plenty of questions remain.<br/><br/>What are the cancer types where exercise makes a difference? How significant is that impact? And what, exactly, defines a physical activity pattern powerful enough to move the needle on cancer risk?<br/><br/>Here’s an overview of the state of the evidence.</p> <h2>Exercise and Cancer Types: A Mixed Bag</h2> <p>When it comes to cancer prevention strategies, guidelines uniformly endorse less couch time and more movement. But a deeper look at the science reveals a complex and often poorly understood connection between exercise and cancer risk.</p> <p>For certain cancer types, the benefits of exercise on cancer risk seem fairly well established.<br/><br/>The latest edition of the <a href="https://health.gov/our-work/nutrition-physical-activity/physical-activity-guidelines">Physical Activity Guidelines for Americans</a>, published in 2018, cites “strong evidence” that regular exercise might curb the risks for breast and colon cancers as well as bladder, endometrial, esophageal, kidney, and gastric cancers. These guidelines also point to “moderate”-strength evidence of a protective association with lung cancer.<br/><br/>The evidence of a protective effect, however, is strongest for breast and colon cancers, said Jennifer Ligibel, MD, senior physician in the Breast Oncology Center at Dana-Farber Cancer Institute, Boston, . “But,” she pointed out, “that may be because they’re some of the most common cancers, and it’s been easier to detect an association.”<br/><br/>Guidelines from the American Cancer Society, <a href="https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21591">published</a> in 2020, align with the 2018 recommendations. <br/><br/>“We believe there’s strong evidence to suggest at least eight different types of cancer are associated with physical activity,” said Erika Rees-Punia, PhD, MPH, senior principal scientist, epidemiology and behavioral research at the American Cancer Society.<br/><br/>That view is not universal, however. Current <a href="https://www.wcrf.org/wp-content/uploads/2021/02/Summary-of-Third-Expert-Report-2018.pdf">recommendations</a> from the World Cancer Research Fund and American Institute for Cancer Research, for example, are more circumspect, citing only three cancers with good evidence of a protective effect from exercise: Breast (postmenopausal), colon, and endometrial.<br/><br/>“We definitely can’t say exercise reduces the risk of all cancers,” said Lee Jones, PhD, head of the Exercise Oncology Program at Memorial Sloan Kettering Cancer Center in New York City. “The data suggest it’s just not that simple.”<br/><br/>And it’s challenging to put all the evidence together, Dr. Jones added.<br/><br/>The physical activity guidelines are based on published systematic reviews, meta-analyses, and pooled analyses of data from observational studies that examined the relationship between physical activity — aerobic exercise, specifically — and cancer incidence. That means the evidence comes with all the limitations observational studies entail, such as how they collect information on participants’ exercise habits — which, Dr. Jones noted, is typically done via “monster questionnaires” that gauge physical activity in broad strokes.<br/><br/>Pooling all those findings into a meta-analysis is tricky, Dr. Jones added, because individual studies vary in important ways — from follow-up periods to how they quantify exercise and track cancer incidence.<br/><br/>In <span class="Hyperlink"><a href="https://pubmed.ncbi.nlm.nih.gov/38181796/">a study</a></span> published in February in <em>Cancer Cell</em>, Dr. Jones and his colleagues attempted to address some of those issues by leveraging data from the PLCO screening trial.<br/><br/>The PLCO was a prospective study of over 60,000 US adults that compared the effects of annual screening vs usual care on cancer mortality. At enrollment, participants completed questionnaires that included an assessment of “vigorous” exercise. Based on that, Dr. Jones and his colleagues classified 55% as “exercisers” — meaning they reported 2 or more hours of vigorous exercise per week. The remaining 45%, who were in the 0 to 1 hour per week range, were deemed non-exercisers.<br/><br/>Over a median of 18 years, nearly 16,000 first-time invasive cancers were diagnosed, and some interesting differences between exercisers and non-exercisers emerged. The active group had lower risks for three cancers: Head and neck, with a 26% lower risk (hazard ratio [HR], 0.74), lung (a 20% lower risk), and breast (an 11% lower risk).<br/><br/>What was striking, however, was the lack of connection between exercise and many cancers cited in the guidelines, including colon, gastric, bladder, endometrial, and renal cancers.<br/><br/>Perhaps even more surprising — exercisers had higher risks for prostate cancer (12%) and melanoma (20%). This finding, Dr. Jones said, is in line with a <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2521826">previous</a> pooled analysis of data from 12 US and European prospective cohorts. In this study, the most physically active participants (90th percentile) had higher risks for melanoma and prostate cancer, compared with the least active group (10th percentile).<br/><br/>The melanoma findings do make sense, Dr. Jones said, given that highly active people may spend a lot of time in the sun. “My advice,” Dr. Jones said, “is, if you’re exercising outside, wear sunscreen.” The prostate cancer findings, however, are more puzzling and warrant further research, he noted.<br/><br/>But the bottom line is that the relationship between exercise and cancer types is mixed and far from nailed down.</p> <h2>How Big Is the Effect?</h2> <p>Even if exercise reduces the risk for only certain cancers, that’s still important, particularly when those links appear strongest for common cancer types, such as breast and colon.</p> <p>But how much of a difference can exercise make?<br/><br/>Based on the evidence, it may only be a modest one. A 2019 systematic <a href="https://journals.lww.com/acsm-msse/fulltext/2019/06000/physical_activity_in_cancer_prevention_and.20.aspx">review</a> by the Physical Activity Guidelines Advisory Committee provided a rough estimate: Across hundreds of epidemiological studies, people with the highest physical activity levels had a 10%-20% lower risk for the cancers cited in the 2018 exercise guidelines compared with people who were least active.<br/><br/>These figures, however, are probably an underestimate, said Anne McTiernan, MD, PhD, a member of the advisory committee and professor of epidemiology, at Fred Hutchinson Cancer Center, Seattle.<br/><br/>“This is what we usually see when a factor is not measured very well,” said Dr. McTiernan, explaining that the individual studies differed in their categories of “highest” and “lowest” physical activity, such that one study’s “highest” could be another’s mid-range.<br/><br/>“In other words, the effects of physical activity are likely larger” than the review found, Dr. McTiernan said.<br/><br/>The next logical question is whether a bigger exercise “dose” — more time or higher intensity — would have a greater impact on cancer risk. A <span class="Hyperlink"><a href="https://ascopubs.org/doi/full/10.1200/JCO.19.02407">2019 study</a></span> published in the <em>Journal of Clinical Oncology</em> tried to clarify that by pooling data on over 750,000 participants from nine prospective cohorts.<br/><br/>Overall, people meeting government recommendations for exercise — equivalent to about 2.5-5 hours of weekly moderate activity, such as a brisk walk, or about 1.25-2.5 hours of more vigorous activities, like running — had lower risks for seven of 15 cancer types studied compared with less active people.<br/><br/>For cancers with positive findings, being on the higher end of the recommended 2.5- to 5-hour weekly range was better. Risk reductions for breast cancer, for instance, were 6% at 2.5 hours of physical activity per week and 10% at 5 hours per week. Similar trends emerged for other cancer types, including colon (8%-14%), endometrial (10%-18%), liver cancer (18%-27%), and non-Hodgkin lymphoma in women (11%-18%).<br/><br/>But there may be an exercise sweet spot that maximizes the cancer risk benefit.<br/><br/>Among people who surpassed the recommendations — exercising for more time or more intensely — the risk reduction benefit did not necessarily improve in a linear fashion. For certain cancer types, such as colon and endometrial, the benefits of more vigorous exercise “eroded at higher levels of activity,” the authors said.<br/><br/>The issue here is that most studies have not dug deeply into aerobic exercise habits. Often, studies present participants with a list of activities — walking, biking, and running — and ask them to estimate how often and for what duration they do each.<br/><br/>Plus, “we’ve usually lumped moderate and vigorous activities together,” Dr. Rees-Punia said, which means there’s a lack of “granular data” to say whether certain intensities or frequencies of exercise are optimal and for whom.</p> <h2>Why Exercise May Lower Cancer Risk</h2> <p>Exercise habits do not, of course, exist in a vacuum. Highly active people, Dr. Ligibel said, tend to be of higher socioeconomic status, leaner, and have generally healthier lifestyles than sedentary people.</p> <p>Body weight is a big confounder as well. However, Dr. Rees-Punia noted, it’s also probably a reason that exercise is linked to lower cancer risks, particularly by preventing weight gain. Still, studies have found that the association between exercise and many cancers remains <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2521826">significant</a> after adjusting for body mass index.<br/><br/>The why remains unclear, though some studies offer clues.<br/><br/>“There’s been some really interesting mechanistic research, suggesting that exercise may help inhibit tumor growth or upregulate the immune system,” Dr. Ligibel said.<br/><br/>That includes not only lab research but small intervention studies. While these studies have <a href="https://www.sciencedirect.com/science/article/abs/pii/S0889159119304428">largely</a> involved people who already have cancer, some have also focused on healthy individuals.<br/><br/>A <a href="https://pubmed.ncbi.nlm.nih.gov/31018921/">2019 study</a> from Dr. Ligibel and her colleagues, which randomly assigned 49 women newly diagnosed with breast cancer to start either an exercise program or mind-body practices ahead of surgery, found exercisers, who had been active for about a month at the time of surgery, showed signs of immune system upregulation in their tumors, while the control group did not.<br/><br/>Among healthy postmenopausal women, a meta-analysis of six clinical trials from Dr. McTiernan and her colleagues <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090977/">found</a> that exercise plus calorie reduction can reduce levels of breast cancer-related endogenous hormones, more so than calorie-cutting alone. And a 2023 <a href="https://aacrjournals.org/clincancerres/article/29/21/4361/729641/Exercise-Training-Reduces-the-Inflammatory">study</a> found that high-intensity exercise boosted the ranks of certain immune cells and reduced inflammation in the colon among people at high risk for colon and endometrial cancers due to <a href="https://emedicine.medscape.com/article/188613-overview">Lynch syndrome</a>.</p> <h2>Defining an Exercise ‘Prescription’</h2> <p>Despite the gaps and uncertainties in the research, government guidelines as well as those from the American Cancer Society and other medical groups are in lockstep in their exercise recommendations: Adults should strive for 150-300 minutes of moderate-intensity aerobic exercise (like brisk walking), 75-150 minutes of vigorous activity (like running), or some combination each week.</p> <p>The guidelines also encourage strength training twice a week — advice that’s based on research tying those activity levels to lower risks for heart disease, diabetes, and other chronic conditions.<br/><br/>But there’s no “best” exercise prescription for lowering cancer risk specifically. Most epidemiological studies have examined only aerobic activity, Dr. Rees-Punia said, and there’s very little known about whether strength conditioning or other moderate heart rate-elevating activities, such as daily household chores, may reduce the risk for cancer.<br/><br/>Given the lack of nuance in the literature, it’s hard to say what intensities, types, or amounts of exercise are best for each individual.<br/><br/>Going forward, device-based measurements of physical activity could “help us sort out the effects of different intensities of exercise and possibly types,” Dr. Rees-Punia said.<br/><br/>But overall, Dr. McTiernan said, the data do show that the risks for several cancers are lower at the widely recommended activity levels.<br/><br/>“The bottom-line advice is still to exercise at least 150 minutes per week at a moderate-intensity level or greater,” Dr. McTiernan said.<br/><br/>Or put another way, moving beats being sedentary. It’s probably wise for everyone to sit less, noted Dr. Rees-Punia, for overall health and based on <span class="Hyperlink"><a href="https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21591">evidence</a></span> tying sedentary time to the risks for certain cancers, including colon, endometrial, and lung.<br/><br/>There’s a practical element to consider in all of this: What physical activities will people actually do on the regular? In the big epidemiological studies, Dr. McTiernan noted, middle-aged and older adults most often report walking, suggesting that’s the preferred, or most accessible activity, for many.<br/><br/>“You can only benefit from the physical activity you’ll actually do,” Dr. Rees-Punia said.<br/><br/>Dr. Ligibel echoed that sentiment, saying she encourages patients to think about physical activity as a process: “You need to find things you like to do and work them into your daily life, in a sustainable way.<br/><br/>“People often talk about exercise being medicine,” Dr. Ligibel said. “But I think you could take that too far. If we get too prescriptive about it, that could take the joy away.”</p> <p> <em>A version of this article appeared on <span class="Hyperlink"><a href="https://www.medscape.com/viewarticle/does-exercise-reduce-cancer-risk-its-just-not-simple-2024a10004g0">Medscape.com</a></span>.</em> </p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>