Healthy Lifestyle May Protect Against Lethal Prostate Cancer In Men At High Genetic Risk

Maintaining a healthy lifestyle may reduce the risk of lethal prostate cancer in men at high genetic risk for developing the disease, according to new research.

"The decreased risk of aggressive disease in those with a favorable lifestyle may suggest that the excess genetic risk of lethal prostate cancer could be offset by adhering to a healthy lifestyle," Dr. Anna Plym said in a statement from the American Association for Cancer Research (AACR) virtual annual meeting, where the findings were presented.

Inherited genetic factors contribute significantly to prostate-cancer risk, explaining 58% of the variability in the disease, Dr. Plym, of Brigham and Women's Hospital in Boston, noted during a conference press briefing.

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Using a validated polygenic risk score for overall prostate cancer, the researchers quantified the genetic risk for prostate cancer in more than 10,000 men in the Health Professionals Follow-up Study.

They applied a validated lifestyle score for lethal prostate cancer (healthy weight, vigorous physical activity, not smoking, and high intake of tomatoes, fatty fish, and reduced intake of processed meat) and examined the incidence of overall and lethal (metastatic disease or prostate-cancer-specific death) prostate cancer.

The researchers identified 2,111 overall prostate-cancer cases during a median follow-up period of 18 years and 238 cases of lethal prostate cancer during a median follow-up of 22 years.

Men with the highest polygenic risk scores had a 5.4-fold increased risk of overall prostate cancer and a 3.5-fold increased risk of lethal prostate cancer compared with their peers with the lowest polygenic risk scores.

The findings suggest that the polygenic risk score "could be used as part of a risk stratification tool for prostate cancer," Dr. Plym, also of Harvard T. H. Chan School of Public Health, told the briefing.

Among men with the highest genetic risk, maintaining a healthy lifestyle was not tied to a lower genetic risk of lethal disease (HR, 0.54; 95% confidence interval, 0.31 to 0.94), but not a lower genetic risk of overall prostate cancer (hazard ratio, 1.01; 95% CI, 0.84 to 1.22), compared with the least healthy lifestyle.

In men with the highest genetic risk, having a healthy lifestyle at baseline was associated with a lifetime cumulative incidence of lethal prostate cancer of 3%, lower than for men having the least healthy lifestyle (6%) and similar to the population average (3%), the authors report in their conference abstract.

"While further studies are needed, this suggests that modifiable factors can mitigate the consequences of having a genetic susceptibility to prostate cancer," Dr. Plym told the briefing.

She cautioned that the study was observational precluding any conclusions about the causal relationship between healthy lifestyles and prostate cancer.

Briefing moderator Dr. Charles Swanton of University College London (UCL) Cancer Institute in the U.K. said, "we need future validation in larger cohorts using similar thresholds and a biological mechanism that might explain an interaction between the healthy lifestyle and a highest genetic risk and the risk of lethal prostate cancer."

—Megan Brooks

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