title: Do environmental factors modify the genetic risk of prostate cancer?
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.
  
  
  CONCLUSIONS
  The effect of genetic factors on prostate cancer risk may vary by lifestyle interventions.
authors.affiliation: Department of Urology, New York University, New York, New York. Population Health, New York University, New York, New York. stacyloeb@gmail.com.
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Peskoe
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Joshu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Huang
authors.affiliation: Population Health, New York University, New York, New York.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: H Ballentine
authors.initials: HB
authors.lastname: Carter
authors.affiliation: Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
mesh_terms: D000368:Aged; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors