title: Pesticide exposure and inherited variants in vitamin d pathway genes in relation to prostate cancer.
abstract: BACKGROUND
  Vitamin D and its metabolites are believed to impede carcinogenesis by stimulating cell differentiation, inhibiting cell proliferation, and inducing apoptosis. Certain pesticides have been shown to deregulate vitamin D's anticarcinogenic properties. We hypothesize that certain pesticides may be linked to prostate cancer via an interaction with vitamin D genetic variants.
  
  
  METHODS
  We evaluated interactions between 41 pesticides and 152 single-nucleotide polymorphisms (SNP) in nine vitamin D pathway genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of Caucasian pesticide applicators within the Agricultural Health Study. We assessed Pinteraction values using likelihood ratio tests from unconditional logistic regression and a false discovery rate (FDR) to account for multiple comparisons.
  
  
  RESULTS
  Five significant interactions (P < 0.01) displayed a monotonic increase in prostate cancer risk with individual pesticide use in one genotype and no association in the other. These interactions involved parathion and terbufos use and three vitamin D genes (VDR, RXRB, and GC). The exposure-response pattern among participants with increasing parathion use with the homozygous CC genotype for GC rs7041 compared with unexposed participants was noteworthy [low vs. no exposure: OR, 2.58, 95% confidence interval (CI), 1.07-6.25; high vs. no exposure: OR, 3.09, 95% CI, 1.10-8.68; Pinteraction = 3.8 × 10(-3)].
  
  
  CONCLUSIONS
  In this study, genetic variations in vitamin D pathway genes, particularly GC rs7041, an SNP previously linked to lower circulating vitamin D levels, modified pesticide associations with prostate cancer risk.
  
  
  CONCLUSIONS
  Because our study is the first to examine this relationship, additional studies are needed to rule out chance findings.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD 20852, USA. karamis@mail.nih.gov
authors.forename: Sara
authors.initials: S
authors.lastname: Karami
authors.forename: Gabriella
authors.initials: G
authors.lastname: Andreotti
authors.forename: Stella
authors.initials: S
authors.lastname: Koutros
authors.forename: Kathryn Hughes
authors.initials: KH
authors.lastname: Barry
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
authors.forename: Summer
authors.initials: S
authors.lastname: Han
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hoppin
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.forename: Jay H
authors.initials: JH
authors.lastname: Lubin
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Burdette
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Yuenger
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Laura E Beane
authors.initials: LE
authors.lastname: Freeman
authors.forename: Aaron
authors.initials: A
authors.lastname: Blair
authors.forename: Michael C R
authors.initials: MC
authors.lastname: Alavanja
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016022:Case-Control Studies; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010575:Pesticides / Q000506:poisoning*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D014807:Vitamin D / Q000235:genetics* / Q000378:metabolism
chemical_list: D010575:Pesticides; D014807:Vitamin D