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. 2015 Jan;24(1):213-20.
doi: 10.1158/1055-9965.EPI-14-0786-T. Epub 2014 Oct 23.

Do environmental factors modify the genetic risk of prostate cancer?

Stacy Loeb  1 , Sarah B Peskoe  2 , Corinne E Joshu  2 , Wen-Yi Huang  3 , Richard B Hayes  4 , H Ballentine Carter  5 , William B Isaacs  5 , Elizabeth A Platz  6
Affiliations

Do environmental factors modify the genetic risk of prostate cancer?

Stacy Loeb et al. Cancer Epidemiol Biomarkers Prev. 2015 Jan.

Abstract

Background: Many SNPs influence prostate cancer 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 prostate cancer in 1,230 incident prostate cancer cases and 1,361 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 prostate cancer 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 prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the 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 (Pinteraction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with <12 alleles and nonusers, the OR for ≥12 alleles was 2.25 (1.69-3.00) in nonusers and 1.70 (1.25-2.32) in users (Pinteraction = 0.009). This pattern was similar for ibuprofen (Pinteraction = 0.023) and vegetables (Pinteraction = 0.010).

Conclusions: This study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer.

Impact: The effect of genetic factors on prostate cancer risk may vary by lifestyle interventions.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

S. Loeb has received speakers’ bureau honoraria from Sanofi IGUCC meeting and Bayer lecture at Colombian Urologic. No potential conflicts of interest were disclosed by the other authors.

Figures

Figure 1
Figure 1
OR of nonadvanced prostate cancer for joint categories of number of risk alleles and aspirin use, PLCO. ORs are adjusted for age (continuous) and education (dichotomous by college degree). The categories for number of risk alleles are approximate quintiles in controls. The median and mode are both 12 risk alleles in the controls.
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