Mark R. Goldstein, MD, FACP

To the Editor: In their paper on colorectal cancer screening, Mankaney and colleagues noted the increasing rates of colorectal cancer in young adults in the United States.¹ Recent epidemiologic data demonstrate an increasing incidence of the disease in people ages 40 through 49 since the mid-1990s.² Even though screening starting at age 45 is not uniformly accepted,¹ there is evidence supporting earlier screening.

During the mid-1990s, the US government mandated that all enriched flour and uncooked cereal grains were to be fortified with folic acid in order to prevent births complicated by neural tube defects.³ Subsequently, there was a 2-fold increase in plasma folate concentrations and, disturbingly, a temporally associated significant increase in the incidence of colorectal cancer.³

Notably, a US trial⁴ testing the efficacy of folic acid 1 mg taken daily for 6 years to prevent colorectal adenomas in those with a history of colorectal adenomas failed to show a reduction in adenoma risk. Instead, participants randomized to folic acid exhibited a significantly increased risk of an advanced adenoma. Another trial,⁵ conducted in the Netherlands, where there is no mandatory folic acid fortification, investigated folic acid 400 µg and vitamin B₁₂ 500 µg daily over 2 to 3 years for the prevention of osteoporotic fractures. The group randomized to the vitamins had a nearly 2-fold increase in the risk of colorectal cancer.

Folic acid can be a double-edged sword.^3,5 Although folic acid intake may protect against carcinogenesis through increased genetic stability, if precancerous or neoplastic cells are present, excess folic acid may promote cancer by increasing DNA synthesis and cell proliferation. Cancer cells have folic acid receptors.

Since screening colonoscopy is typically done in individuals over 50, advanced adenomas from folic acid exposure in people younger than 50 likely go undiagnosed. Therefore, colorectal cancer screening should start at a younger age in countries where folic acid fortification is mandatory.

To the Editor: In their paper on colorectal cancer screening, Mankaney and colleagues noted the increasing rates of colorectal cancer in young adults in the United States.¹ Recent epidemiologic data demonstrate an increasing incidence of the disease in people ages 40 through 49 since the mid-1990s.² Even though screening starting at age 45 is not uniformly accepted,¹ there is evidence supporting earlier screening.

During the mid-1990s, the US government mandated that all enriched flour and uncooked cereal grains were to be fortified with folic acid in order to prevent births complicated by neural tube defects.³ Subsequently, there was a 2-fold increase in plasma folate concentrations and, disturbingly, a temporally associated significant increase in the incidence of colorectal cancer.³

Notably, a US trial⁴ testing the efficacy of folic acid 1 mg taken daily for 6 years to prevent colorectal adenomas in those with a history of colorectal adenomas failed to show a reduction in adenoma risk. Instead, participants randomized to folic acid exhibited a significantly increased risk of an advanced adenoma. Another trial,⁵ conducted in the Netherlands, where there is no mandatory folic acid fortification, investigated folic acid 400 µg and vitamin B₁₂ 500 µg daily over 2 to 3 years for the prevention of osteoporotic fractures. The group randomized to the vitamins had a nearly 2-fold increase in the risk of colorectal cancer.

Folic acid can be a double-edged sword.^3,5 Although folic acid intake may protect against carcinogenesis through increased genetic stability, if precancerous or neoplastic cells are present, excess folic acid may promote cancer by increasing DNA synthesis and cell proliferation. Cancer cells have folic acid receptors.

Since screening colonoscopy is typically done in individuals over 50, advanced adenomas from folic acid exposure in people younger than 50 likely go undiagnosed. Therefore, colorectal cancer screening should start at a younger age in countries where folic acid fortification is mandatory.

To the Editor: In their paper on colorectal cancer screening, Mankaney and colleagues noted the increasing rates of colorectal cancer in young adults in the United States.¹ Recent epidemiologic data demonstrate an increasing incidence of the disease in people ages 40 through 49 since the mid-1990s.² Even though screening starting at age 45 is not uniformly accepted,¹ there is evidence supporting earlier screening.

During the mid-1990s, the US government mandated that all enriched flour and uncooked cereal grains were to be fortified with folic acid in order to prevent births complicated by neural tube defects.³ Subsequently, there was a 2-fold increase in plasma folate concentrations and, disturbingly, a temporally associated significant increase in the incidence of colorectal cancer.³

Notably, a US trial⁴ testing the efficacy of folic acid 1 mg taken daily for 6 years to prevent colorectal adenomas in those with a history of colorectal adenomas failed to show a reduction in adenoma risk. Instead, participants randomized to folic acid exhibited a significantly increased risk of an advanced adenoma. Another trial,⁵ conducted in the Netherlands, where there is no mandatory folic acid fortification, investigated folic acid 400 µg and vitamin B₁₂ 500 µg daily over 2 to 3 years for the prevention of osteoporotic fractures. The group randomized to the vitamins had a nearly 2-fold increase in the risk of colorectal cancer.

Folic acid can be a double-edged sword.^3,5 Although folic acid intake may protect against carcinogenesis through increased genetic stability, if precancerous or neoplastic cells are present, excess folic acid may promote cancer by increasing DNA synthesis and cell proliferation. Cancer cells have folic acid receptors.

Since screening colonoscopy is typically done in individuals over 50, advanced adenomas from folic acid exposure in people younger than 50 likely go undiagnosed. Therefore, colorectal cancer screening should start at a younger age in countries where folic acid fortification is mandatory.

To the Editor: We read with interest the article by Cikach et al on thoracic aortic aneurysm.¹ For medical management of this condition, the authors emphasized controlling blood pressure and heart rate and also avoiding isometric exercises and heavy lifting. In addition to their recommendations, we believe there is plausible evidence to advise caution if fluoroquinolone antibiotics are used in this setting.

Three large population-based studies, from Canada,² Taiwan,³ and Sweden,⁴ collectively demonstrated a significant 2-fold increase in the incidence of aortic aneurysm and dissection presenting within 60 days of fluoroquinolone use compared with other antibiotic exposure. Moreover, a longer duration of fluoroquinolone use was associated with a significantly higher incidence of aortic aneurysm and dissection.³

Mechanistically, fluoroquinolones have been shown to up-regulate production of several matrix metalloproteinases, including metalloproteinase 2, leading to degradation of type I collagen.^2,5 Type I and type III are the dominant collagens in the aortic wall, and collagen degradation is implicated in aortic aneurysm formation and expansion.

Fluoroquinolones are widely prescribed in both outpatient and inpatient settings and are sometimes used for long durations in the geriatric population.² It is possible that these drugs have a propensity to increase aortic aneurysm expansion and dissection in older patients who already have aortic aneurysm. Accordingly, this might make the risk-benefit ratio unfavorable for using these drugs in these situations, and other antibiotics should be used, if indicated.

Furthermore, if fluoroquinolones are used in patients with aortic aneurysm, perhaps imaging studies of the aneurysm should be done more frequently than once a year to detect accelerated aneurysm growth. Finally, physicians should be aware of the possibility of increased aortic aneurysm expansion and dissection with fluoroquinolone use.

To the Editor: We read with interest the article by Cikach et al on thoracic aortic aneurysm.¹ For medical management of this condition, the authors emphasized controlling blood pressure and heart rate and also avoiding isometric exercises and heavy lifting. In addition to their recommendations, we believe there is plausible evidence to advise caution if fluoroquinolone antibiotics are used in this setting.

Three large population-based studies, from Canada,² Taiwan,³ and Sweden,⁴ collectively demonstrated a significant 2-fold increase in the incidence of aortic aneurysm and dissection presenting within 60 days of fluoroquinolone use compared with other antibiotic exposure. Moreover, a longer duration of fluoroquinolone use was associated with a significantly higher incidence of aortic aneurysm and dissection.³

Mechanistically, fluoroquinolones have been shown to up-regulate production of several matrix metalloproteinases, including metalloproteinase 2, leading to degradation of type I collagen.^2,5 Type I and type III are the dominant collagens in the aortic wall, and collagen degradation is implicated in aortic aneurysm formation and expansion.

Fluoroquinolones are widely prescribed in both outpatient and inpatient settings and are sometimes used for long durations in the geriatric population.² It is possible that these drugs have a propensity to increase aortic aneurysm expansion and dissection in older patients who already have aortic aneurysm. Accordingly, this might make the risk-benefit ratio unfavorable for using these drugs in these situations, and other antibiotics should be used, if indicated.

Furthermore, if fluoroquinolones are used in patients with aortic aneurysm, perhaps imaging studies of the aneurysm should be done more frequently than once a year to detect accelerated aneurysm growth. Finally, physicians should be aware of the possibility of increased aortic aneurysm expansion and dissection with fluoroquinolone use.

To the Editor: We read with interest the article by Cikach et al on thoracic aortic aneurysm.¹ For medical management of this condition, the authors emphasized controlling blood pressure and heart rate and also avoiding isometric exercises and heavy lifting. In addition to their recommendations, we believe there is plausible evidence to advise caution if fluoroquinolone antibiotics are used in this setting.

Three large population-based studies, from Canada,² Taiwan,³ and Sweden,⁴ collectively demonstrated a significant 2-fold increase in the incidence of aortic aneurysm and dissection presenting within 60 days of fluoroquinolone use compared with other antibiotic exposure. Moreover, a longer duration of fluoroquinolone use was associated with a significantly higher incidence of aortic aneurysm and dissection.³

Mechanistically, fluoroquinolones have been shown to up-regulate production of several matrix metalloproteinases, including metalloproteinase 2, leading to degradation of type I collagen.^2,5 Type I and type III are the dominant collagens in the aortic wall, and collagen degradation is implicated in aortic aneurysm formation and expansion.

Fluoroquinolones are widely prescribed in both outpatient and inpatient settings and are sometimes used for long durations in the geriatric population.² It is possible that these drugs have a propensity to increase aortic aneurysm expansion and dissection in older patients who already have aortic aneurysm. Accordingly, this might make the risk-benefit ratio unfavorable for using these drugs in these situations, and other antibiotics should be used, if indicated.

Furthermore, if fluoroquinolones are used in patients with aortic aneurysm, perhaps imaging studies of the aneurysm should be done more frequently than once a year to detect accelerated aneurysm growth. Finally, physicians should be aware of the possibility of increased aortic aneurysm expansion and dissection with fluoroquinolone use.