Healthy lifestyle may help prevent lethal prostate cancer among men with high genetic risk

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Men with a high genetic risk for prostate cancer had a lower likelihood of developing lethal disease if they adhered to a healthy lifestyle, according to data presented at the virtual American Association for Cancer Research Annual Meeting.

“We recently validated a 269 genetic-variant polygenic risk score for prostate cancer and found that among men in the highest polygenic risk score group, over 50% had been diagnosed with prostate cancer by age 85 [years],” Anna Plym, PhD, postdoctoral research fellow at Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, told Healio. “This excess risk [for] prostate cancer among men with a high polygenic risk score motivated us to initiate a study on possible lifestyle factors that can mitigate this increased risk. From previous research, we have increasing evidence that a healthy lifestyle may reduce the risk [for] lethal prostate cancer but, until now, it has been unclear how this relates to men at high genetic risk.”

Plym and colleagues used their polygenic risk score to quantify the genetic risk for prostate cancer among 10,443 men with genotype data available from the Health Professionals Follow-up Study. The researchers then applied a validated time-varying lifestyle score for lethal prostate cancer — for which a score of 1 to 2 indicated least healthy, 3 indicated moderately healthy, and 4 to 6 indicated most healthy — that included healthy weight, not smoking, vigorous physical activity and diet (high consumption of tomatoes and fatty fish and reduced intake of processed meat).

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

Results showed men in the highest risk quartile based on their polygenic risk score had a 5.4 times higher likelihood of developing prostate cancer (HR = 5.39; 95% CI, 4.59-6.33) and a 3.5 times higher likelihood of developing lethal prostate cancer (HR = 3.53; 95% CI, 2.34-5.32) than those in the lowest risk quartile.

Among men in the highest genetic risk quartile, those who adhered to the healthiest lifestyle demonstrated a significantly lower risk for lethal prostate cancer (HR = 0.54; 95% CI, 0.31-0.93) than those who had the least healthy lifestyle. A moderately healthy lifestyle also conferred a reduction in risk for lethal prostate cancer among men at highest genetic risk (HR = 0.59; 95% CI, 0.36-0.95).

Although men at highest genetic risk who adhered to the healthiest lifestyle did not have a decreased risk for overall prostate cancer (HR = 1.01; 95% CI, 0.84-1.22), these men had a lifetime cumulative incidence of lethal prostate cancer that was half that of men with the least healthy lifestyle (3% vs. 6%) and similar to that of the entire study population.

“Our key message is that a healthy lifestyle may be of particular benefit for men at increased genetic risk for prostate cancer, possibly cutting the risk [for] disease progression by half,” Plym told Healio. “If confirmed by further research, in particular within other populations, these recommendations can be put forward for men with a known family history of prostate cancer and, when germline genetic testing is more widely available, for men with a high polygenic risk score, too.

Plym added that although the results are encouraging, the observational design of the study means the findings could have been influenced by other factors associated with a healthy lifestyle.

Long-term goals for further research include a randomized trial of lifestyle interventions in men at increased genetic risk, according to Plym. But, first, the researchers plan to validate their findings in more populations of men, particularly those of non-European ancestry.

“Given their higher burden of prostate cancer, we are particularly interested to what extent men of African ancestry at high genetic risk can reduce their risk by adhering to a healthy lifestyle,” Plym said.

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