Conference Coverage

Healthy lifestyle may offset genetic risk in prostate cancer


 

FROM AACR 2021

Adhering to a healthy lifestyle may offset the heightened risk of lethal prostate cancer in patients with adverse genetic risk factors, according to results of a large U.S. study.

In men at the highest risk of dying from prostate cancer, having the highest healthy lifestyle scores cut the risk of fatal disease in half, said study author Anna Plym, PhD, of Brigham and Women’s Hospital and Harvard School of Public Health, both in Boston. She presented these findings at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract 822).

Dr. Plym noted that about 58% of the variability in prostate cancer risk is accounted for by genetic factors, with common single-nucleotide polymorphisms (SNPs) accounting for a substantial proportion of prostate cancer susceptibility.

A recent study showed that a polygenic risk score (PRS) derived by combining information from 269 SNPs was “highly predictive” of prostate cancer, Dr. Plym said. There was a 10-fold gradient in disease risk between the lowest and highest genetic risk deciles, and the pattern was consistent across ethnic groups.

In addition, Dr. Plym noted, previous studies have suggested that a healthy lifestyle reduces lethal prostate cancer risk.

What has remained unclear is whether the risk for both developing prostate cancer and experiencing progression to lethal disease can be offset by adherence to a healthy lifestyle.

To investigate, Dr. Plym and colleagues used the 269-SNP PRS to quantify the genetic risk of prostate cancer in 10,443 men enrolled in the Health Professionals Follow-up Study. The men were divided into quartiles according to genetic risk.

The investigators also classified the men using a validated lifestyle score. For this score, one point was given for each of the following: not currently smoking or having quit 10 or more years ago, body mass index under 30 kg/m2, high vigorous physical activity, high intake of tomatoes and fatty fish, and low intake of processed meat. Patients with 1-2 points were considered the least healthy, those with 3 points were moderately healthy, and those with 4-6 points were the most healthy.

The outcomes assessed were overall prostate cancer and lethal prostate cancer (i.e., metastatic disease or prostate cancer–specific death).

No overall benefit of healthy lifestyle

At a median follow-up of 18 years, 2,111 cases of prostate cancer were observed. And at a median follow-up of 22 years, 238 lethal prostate cancer events occurred.

Men in the highest genetic risk quartile were five times more likely to develop prostate cancer (hazard ratio, 5.39; 95% confidence interval, 4.59-6.34) and three times more likely to develop lethal prostate cancer (HR, 3.43; 95% CI, 2.29-5.14), when compared with men in the lowest genetic risk quartile.

Adherence to a healthy lifestyle did not decrease the risk of prostate cancer overall (HR, 1.01; 95% CI, 0.84-1.22), nor did it affect men in the lower genetic risk quartiles.

However, healthy lifestyle did appear to affect men in the highest genetic risk quartile. Men with the highest healthy lifestyle scores had roughly half the risk of lethal prostate cancer, compared to men with the lowest lifestyle scores (3% vs. 6%).

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