Do Environmental Factors Modify the Genetic Risk of Prostate Cancer?

Background: Many single nucleotide polymorphisms (SNPs) influence prostate cancer (PCa) risk. To what extent genetic risk can be reduced by environmental factors is unknown. Methods: We evaluated effect modification by environmental factors of the association between susceptibility SNPs and PCa in 1,230 incident PCa cases and 1,362 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (≥12 SNPs) and PCa within environmental factor strata and tested for interaction. Results: Men with ≥12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced PCa, respectively. These associations were attenuated with use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced PCa: compared to <12 alleles and no selenium, the odds ratio (OR) for ≥12 alleles was 2.06 (95% confidence interval [CI], 1.67-2.55) in nonusers and 0.99 (0.38-2.58) in users (P-interaction=0.031). Aspirin had the most marked attenuation for nonadvanced PCa: compared to <12 alleles and non-users, the OR for ≥12 alleles was 2.25 (1.69-3.00) in nonusers and 1.70 (1.25-2.32) in users (P-interaction=0.009). This pattern was similar for ibuprofen (P-interaction=0.023) and vegetables (P-interaction=0.010). Conclusions: This study suggests that selenium supplements may reduce genetic risk of advanced PCa, while aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced PCa. Impact:The effect of genetic factors on PCa risk may vary by lifestyle interventions.