By Kurt Samson
A healthy lifestyle might offset the risk of developing a lethal form of prostate cancer, a researcher shared during the 2021 Annual Meeting of the American Association for Cancer Research (AACR) (Abstract 822).
Anna Plym, PhD, a postdoctoral research fellow at Brigham and Women's Hospital and Harvard T. H. Chan School of Public Health, noted that prostate cancer is the most common non-skin cancer detected in men, and the second-leading cause of cancer deaths in men, after lung cancer. Genetic factors account for approximately 58 percent of the variability in prostate cancer risk, she said.
Researchers looked at the genetic data of nearly 10,500 men—2,100 who developed prostate cancer over a median follow-up period of 18 years, and almost 240 whose prostate cancer proved lethal over a median follow-up of 22 years.
The study showed that men in the highest risk quartile, or lowest scores for healthy living according to their polygenic risk score, were 5.4 times more likely to develop prostate cancer and 3.5 times more likely to develop lethal prostate cancer than those in the lowest risk quartile.
“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," said Plym.
“In our study, a healthy lifestyle did not attenuate genetic risk of overall prostate cancer. However, a healthy lifestyle did attenuate the genetic risk of lethal disease in men at highest genetic risk. While further studies are needed, this suggests that modifiable factors can mitigate the consequences of having a genetic susceptibility to prostate cancer," she noted. “While further studies are needed, this suggests that modifiable factors can mitigate the consequences of having a genetic susceptibility to prostate cancer."
Also of note is that, among the men maintaining a healthy lifestyle at study entry who had the highest genetic risk, there was a 3 percent lifetime cumulative occurrence of lethal prostate cancer. This was half of the 6 percent lifetime cumulative incidence for men with the least healthy lifestyle. It is also comparable to the 3 percent population average.
It is unclear however if the increased genetic risk of prostate cancer, including progression to lethal disease, can be offset by adherence to a healthy lifestyle, Plym noted.
The investigators used a validated risk score based on polygenics—those traits with contribution of more than one gene—for overall prostate cancer. They quantified the genetic risk of prostate cancer in 10,443 men in the Health Professionals Follow-up Study for whom genotype data was available.
Next, they applied a validated lifestyle score for lethal prostate cancer which encompassed healthy weight; vigorous physical activity; not smoking; and high consumption of tomatoes, fatty fish, and reduced intake of processed meat. They then examined the incidence of overall and lethal (metastatic disease or prostate cancer-specific death) prostate cancer from the date of blood (1993-1999) or cheek collection (2005-2006) through 2014 (2016 for lethal disease).
In a median follow-up period of 18 years for overall prostate cancer and 22 years for lethal prostate cancer, the researchers identified 2,111 overall prostate cancer cases and 238 lethal prostate cancer cases.
Multivariable Cox proportional-hazards models were used to estimate the risk of overall and lethal prostate cancer by joint categories of genetic risk (PRS quartiles) and a time-varying lifestyle score (1-2: least healthy, 3: moderate healthy, and 4-6: most healthy).
Both unweighted and inverse probability weighted (IPW) models (to account for possible bias arising from the genotype sampling design) were applied. Lifetime cumulative incidence was estimated using regression standardization.
The PRS enabled risk stratification for both overall and lethal prostate cancer, with men in the highest genetic risk quartile having a 5.4-fold increased risk of overall prostate cancer and a 3.5-fold increased risk of lethal prostate cancer compared with men in the lowest genetic risk quartile.
Among men in the highest genetic risk quartile, adhering to a healthy lifestyle was significantly associated with a decreased risk of lethal prostate cancer (HRipw=0.54, 95% CI=0.31- 0.94) compared with the least healthy lifestyle. However, adhering to healthy lifestyle was not associated with a decreased risk of overall prostate cancer (HR=1.01, 95% CI=0.84-1.22).
The researchers then measured the effect of adhering to a healthy lifestyle, and found that among men in the highest-risk quartile, those with the highest healthy lifestyle scores had about half the risk of developing lethal prostate cancer compared with those with the least healthy lifestyle.
In the high-risk group, having a healthy lifestyle at the time of study entry was associated with a lifetime cumulative lethal prostate cancer incidence of 3 percent, compared with 6 percent for high-risk men having the least healthy lifestyle and 3 percent for the study population as a whole.
Adhering to a healthy lifestyle was not associated with a decreased risk of overall prostate cancer, nor did it affect men in the lower genetic risk quartiles, Plym said, adding that further research is necessary to determine why the benefit was limited to lethal prostate cancer risk in men with the highest genetic risk.
One possible explanation for the findings is that the genetic variants that contribute to a high polygenic risk score are also the variants with the strongest interaction with lifestyle factors, according to Plym.
“The study adds to a wide body of cancer prevention research that shows the benefit of a healthy lifestyle, including not smoking, maintaining a healthy weight, getting regular exercise, and eating a healthy diet," she noted, adding that the results of this study underscore the importance of surveillance for those with a genetic predisposition to develop prostate cancer.
“Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable."
Plym noted that the study was observational, and therefore the association between healthy lifestyles and prostate cancer may not be a causal link.
Kurt Samson is a contributing writer.