title: Sun exposure, vitamin D receptor genetic variants, and risk of breast cancer in the Agricultural Health Study.
abstract: BACKGROUND
  Epidemiologic evidence suggests a negative relation between sunlight exposure and breast cancer risk. The hypothesized mechanism is sunlight-induced cutaneous synthesis of vitamin D.
  
  
  OBJECTIVE
  Our goal was to examine sun exposure and its interaction with vitamin D receptor (VDR) gene variants on breast cancer risk.
  
  
  METHODS
  We examined sun exposure and breast cancer incidence among 31,021 private pesticide applicators' wives, including 578 cases, enrolled in the prospective Agricultural Health Study cohort and followed 8.6 years on average. We estimated interactions between sun exposure, VDR variants, and breast cancer in a nested case-control study comprising 293 cases and 586 matched controls. Information on sun exposure was obtained by questionnaire at cohort enrollment. Relative risks were estimated using Cox proportional hazards regression for the cohort data and conditional logistic regression for the nested case-control data.
  
  
  RESULTS
  We observed a small decrease in breast cancer risk in association with usual sun exposure of ≥ 1 hr/day (versus < 1 hr/day) 10 years before the start of follow-up among all participants [hazard ratio (HR) = 0.8; 95% CI: 0.6, 1.0]. The association appeared to be slightly stronger in relation to estrogen receptor-positive tumors (HR = 0.7; 95% CI: 0.5, 0.9) than estrogen receptor-negative tumors (HR = 1.1; 95% CI: 0.6, 2.1). The HR for joint exposure ≥ 1 hr/day of sunlight and one VDR haplotype was less than expected given negative HRs for each individual exposure (interaction p-value = 0.07).
  
  
  CONCLUSIONS
  Our results suggest that sun exposure may be associated with reduced risk of breast cancer, but we did not find clear evidence of modification by VDR variants. Larger studies are warranted, particularly among populations in whom low levels of usual sun exposure can be more precisely characterized.
authors.affiliation: Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Engel
authors.forename: Jaya
authors.initials: J
authors.lastname: Satagopan
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.forename: Urvi
authors.initials: U
authors.lastname: Mujumdar
authors.forename: Joseph
authors.initials: J
authors.lastname: Coble
authors.forename: Pampa
authors.initials: P
authors.lastname: Roy
authors.forename: Sarah
authors.initials: S
authors.lastname: Yoo
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.forename: Michael C
authors.initials: MC
authors.lastname: Alavanja
mesh_terms: D000383:Agriculture; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007484:Iowa / Q000453:epidemiology; D015233:Models, Statistical; D009657:North Carolina / Q000453:epidemiology; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000235:genetics*; D013472:Sunlight
chemical_list: D018167:Receptors, Calcitriol