Healthy lifestyle could reduce lethal prostate cancer risk

Having a healthy lifestyle could reduce the risk of lethal prostate cancer even in men with a high genetic risk for the disease, a recent study showed.

“A healthy lifestyle attenuated the genetic risk of lethal disease in men at highest genetic risk [though it] did not attenuate the genetic risk of overall prostate cancer,” presented study author Dr Anna Plym from Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, US, at AACR 2021.

The study population comprised the 10,443 men enrolled in the Health Professionals Follow-up Study with available genotype data. They were followed up from the time of DNA collection until prostate cancer event, death, or end of follow-up. A validated polygenic risk score (PRS) was used to assess genetic risk for prostate cancer. Healthy lifestyle was assessed using a validated lifestyle score which included healthy weight, vigorous physical activity, not smoking, a high consumption of tomatoes and fatty fish, and a reduced intake of processed meat.

A total of 2,111 cases of prostate cancer were documented over a median 18-year follow-up, and 238 lethal prostate cancer events occurred over a median 22 years.

Increasing PRS score – denoting a high genetic risk – was tied to an increasing risk of both overall and lethal prostate cancer. [AACR 2021, abstract 822]

Compared with the lowest PRS quartile (0–25 percent), those in the 25–50 and 50–75 percent quartiles had an increased risk of overall prostate cancer (hazard ratio [HR], 1.69, 95 percent confidence interval [CI], 1.41–2.03 and HR, 3.02, 95 percent CI, 2.55–3.58, respectively), with a fivefold risk noted in the highest quartile (75–100 percent; HR, 5.39, 95 percent CI, 4.59–6.34).

Similarly, lethal prostate cancer risk was increased with higher PRS quartiles (HR, 1.43, 95 percent CI, 0.91–2.26 [25–50 percent], HR, 2.44, 95 percent CI, 1.61–3.71 [50–75 percent], and HR, 3.43, 95 percent CI, 2.29–5.14 [75–100 percent]) compared with the lowest PRS quartile.

However, when incorporating the lifestyle score, a healthy lifestyle was not associated with a reduced risk of overall prostate cancer regardless of genetic risk, said Plym.

Among men with a PRS of 75–100 percent, compared with men who were the least healthy (scores of 0–2), the HRs for those who were moderately healthy and healthy (scores of 3 and 4–6, respectively) were 0.99 and 1.01, respectively. Among men with a PRS of 0–25 percent, those who were least healthy, moderately healthy, and healthy had HRs of 0.16, 0.18, and 0.22, respectively.

However, there was a reduced risk of lethal prostate cancer among men with the highest genetic risk score (PRS 75–100 percent) who had a healthy lifestyle. Compared with the least healthy men, those who were moderately healthy and healthy almost halved their risk of lethal prostate cancer (HRs, 0.59 and 0.54, respectively).

“This reduced risk was mainly limited to men in the highest genetic risk quartile,” noted Plym. “Among these men, the lifetime risk of lethal disease was 6 percent in the least healthy and 3 percent in the healthiest.”

“The decreased risk of aggressive disease in those with a favourable lifestyle may suggest that the excess genetic risk of lethal prostate cancer could be offset by adhering to a healthy lifestyle,” added Plym.

“[Additionally,] inherited genetic factors captured by this PRS are associated with an increased risk of prostate cancer suggesting that the PRS could be used as part of a risk stratification tool for prostate cancer,” she continued.

“While further studies are needed, [the results] suggest that modifiable factors can mitigate the consequences of having a genetic susceptibility to prostate cancer,” Plym said. “Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening programme, aimed at detecting a potentially lethal prostate cancer while it is still curable,” she concluded.