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Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

McKay, James D.; McCullough, Marjorie L.; Ziegler, Regina G.; Kraft, Peter; Saltzman, Barbara S.; Riboli, Elio; Barricarte, Aurelio; Berg, Christine D.; Berglund, Göran LU and Bingham, Sheila, et al. (2009) In Cancer Epidemiology Biomarkers & Prevention 18(1). p.297-305
Abstract
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), rs154441.0 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokIff 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... (More)
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), rs154441.0 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokIff 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, 1-1.6; 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, 1.1.0; 95% CI, 0.981.24). No association was noted between rs1544410 (Bsm I) 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. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297-305) (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
18
issue
1
pages
297 - 305
publisher
American Association for Cancer Research
external identifiers
  • wos:000262424200039
  • scopus:58349085991
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-08-0539
language
English
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850ab45b-5a68-45b8-8657-aae3449094d7 (old id 1312868)
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2009-03-18 09:04:02
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@article{850ab45b-5a68-45b8-8657-aae3449094d7,
  abstract     = {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), rs154441.0 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokIff 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, 1-1.6; 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, 1.1.0; 95% CI, 0.981.24). No association was noted between rs1544410 (Bsm I) 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. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297-305)},
  author       = {McKay, James D. and McCullough, Marjorie L. and Ziegler, Regina G. and Kraft, Peter and Saltzman, Barbara S. and Riboli, Elio and Barricarte, Aurelio and Berg, Christine D. and Berglund, Göran and Bingham, Sheila and Brustad, Magritt and Bueno-de-Mesquita, H. Bas and Burdette, Laurie and Buring, Julie and Calle, Eugenia E. and Chanock, Stephen J. and Clavel-Chapelon, Francoise and Cox, David G. and Dossus, Laure and Feigelson, Heather Spencer and Haiman, Christopher A. and Hankinson, Susan E. and Hoover, Robert N. and Hunter, David J. and Husing, Anika and Kaaks, Rudolph and Kolonel, Laurence N. and Le Marchand, Loic and Linseisen, Jakob and McCarty, Catherine A. and Overvad, Kim and Panico, Salvatore and Purdue, Mark P. and Stram, Daniel O. and Stevens, Victoria L. and Trichopoulos, Dimitrios and Willett, Walter C. and Yuenger, Jeffrey and Thun, Michael J.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {1},
  pages        = {297--305},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-08-0539},
  volume       = {18},
  year         = {2009},
}