Sunlight, polymorphisms of vitamin D-related genes and risk of breast cancer

Barbara J. Fuhrman, D. Michal Freedman, Parveen Bhatti, Michele M. Doody, Yi Ping Fu, Shih Chen Chang, Martha S. Linet, Alice J. Sigurdson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Background/Aim: 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. Materials and 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, Ptrend=0.005) and one with reduced breast cancer risk (rs1570669, Ptrend=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). Conclusion: 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.

Original languageEnglish
Pages (from-to)543-552
Number of pages10
JournalAnticancer Research
Volume33
Issue number2
StatePublished - Feb 2013
Externally publishedYes

Keywords

  • Breast cancer
  • Case-control
  • Gene
  • Polymorphisms
  • Sunlight
  • Vitamin D

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