title: Sunlight, polymorphisms of vitamin D-related genes and risk of breast cancer.
abstract: OBJECTIVE
  Geographic gradients in breast cancer incidence and mortality suggest that vitamin D may reduce risk. The enzyme 25-hydroxyvitamin D 24-hydroxylase (CYP24A1), which degrades the active form of vitamin D, and the vitamin D receptor (VDR) are both found in breast tissue. We investigated six polymorphisms in CYP24A1 and two in the VDR gene in association with breast cancer risk.
  
  
  METHODS
  We conducted a case-control study within the nationwide U.S. Radiologic Technologists cohort, including 845 controls and 484 incident breast cancer cases. Associations of polymorphic variants and ecologic and personal measures of sun exposure with breast cancer risk were assessed using unconditional logistic regression.
  
  
  RESULTS
  Two polymorphisms in CYP24A1 were associated with increased breast cancer risk (rs34043203, P(trend)=0.03; rs2762934, P(trend)=0.005) and one with reduced breast cancer risk (rs1570669, P(trend)=0.048). Risk was inversely associated with minor alleles for the VDR Bsm1 polymorphism (rs1544410, P(trend)=0.05) but not Fok1 (rs2228570). Sunlight measures were not associated with breast cancer risk, however significant interactions between time outdoors in the teen years and three unlinked genotypes were found for VDR (rs1544410, rs2228570) and CYP24A1 (rs1570669).
  
  
  CONCLUSIONS
  In this nation-wide breast cancer case-control study, we found that the vitamin D pathway was involved in disease etiology and our results further suggest that reduced cancer risk, in association with sunlight, may depend on timing of exposure and genetic background. These findings merit further investigation.
authors: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd MSC 7238, Bethesda, MD 20892-7238, USA.
authors: Barbara J
authors: BJ
authors: Fuhrman
authors: D Michal
authors: DM
authors: Freedman
authors: Parveen
authors: P
authors: Bhatti
authors: Michele M
authors: MM
authors: Doody
authors: Yi-Ping
authors: YP
authors: Fu
authors: Shih-Chen
authors: SC
authors: Chang
authors: Martha S
authors: MS
authors: Linet
authors: Alice J
authors: AJ
authors: Sigurdson
mesh_terms: D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D062306:Geography, Medical; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics*; D013472:Sunlight / Q000009:adverse effects*; D011795:Surveys and Questionnaires; D013997:Time Factors; D014807:Vitamin D / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase
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