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Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

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  • James D McKay, Denmark
  • Marjorie L McCullough, Denmark
  • Regina G Ziegler, Denmark
  • Peter Kraft, Denmark
  • Barbara S Saltzman, Denmark
  • Elio Riboli, Denmark
  • Aurelio Barricarte, Denmark
  • Christine D Berg, Denmark
  • Goran Bergland, Denmark
  • Sheila Bingham, Denmark
  • Magritt Brustad, Denmark
  • H Bas Bueno-de-Mesquita, Denmark
  • Laurie Burdette, Denmark
  • Julie Buring, Denmark
  • Eugenia E Calle, Denmark
  • Stephen J Chanock, Denmark
  • Françoise Clavel-Chapelon, Denmark
  • David G Cox, Denmark
  • Laure Dossus, Denmark
  • Heather Spencer Feigelson, Denmark
  • Christopher A Haiman, Denmark
  • Susan E Hankinson, Denmark
  • Robert N Hoover, Denmark
  • David J Hunter, Denmark
  • Anika Husing, Denmark
  • Rudolph Kaaks, Denmark
  • Laurence N Kolonel, Denmark
  • Loic Le Marchand, Denmark
  • Jakob Linseisen, Denmark
  • Catherine A McCarty, Denmark
  • Kim Overvad
  • Salvatore Panico, Denmark
  • Mark P Purdue, Denmark
  • Daniel O Stram, Denmark
  • Victoria L Stevens, Denmark
  • Dimitrios Trichopoulos, Denmark
  • Walter C Willett, Denmark
  • Jeffrey Yuenger, Denmark
  • Michael J Thun, Denmark
  • Department of Clinical Epidemiology
BACKGROUND: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability. METHODS: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. RESULTS: The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). CONCLUSIONS: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status.
Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Pages (from-to)297-305
Number of pages8
Publication statusPublished - 2009

    Research areas

  • Adult, Aged, Breast Neoplasms, Case-Control Studies, Female, Genotype, Humans, Linkage Disequilibrium, Logistic Models, Middle Aged, Polymorphism, Single Nucleotide, Prospective Studies, Receptors, Calcitriol, Risk

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