TY - JOUR
T1 - Vitamin D receptor polymorphisms and breast cancer risk
T2 - Results from the national cancer institute breast and prostate cancer cohort consortium
AU - McKay, James D.
AU - McCullough, Marjorie L.
AU - Ziegler, Regina G.
AU - Kraft, Peter
AU - Saltzman, Barbara S.
AU - Riboli, Elio
AU - Barricarte, Aurelio
AU - Berg, Christine D.
AU - Bergland, Goran
AU - Bingham, Sheila
AU - Brustad, Magritt
AU - Bueno-de-Mesquita, H. Bas
AU - Burdette, Laurie
AU - Buring, Julie
AU - Calle, Eugenia E.
AU - Chanock, Stephen J.
AU - Clavel-Chapelon, Françoise
AU - Cox, David G.
AU - Dossus, Laure
AU - Feigelson, Heather Spencer
AU - Haiman, Christopher A.
AU - Hankinson, Susan E.
AU - Hoover, Robert N.
AU - Hunter, David J.
AU - Husing, Anika
AU - Kaaks, Rudolph
AU - Kolonel, Laurence N.
AU - Le Marchand, Loic
AU - Linseisen, Jakob
AU - McCarty, Catherine A.
AU - Overvad, Kim
AU - Panico, Salvatore
AU - Purdue, Mark P.
AU - Stram, Daniel O.
AU - Stevens, Victoria L.
AU - Trichopoulos, Dimitrios
AU - Willett, Walter C.
AU - Yuenger, Jeffrey
AU - Thun, Michael J.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-08-0539
DO - 10.1158/1055-9965.EPI-08-0539
M3 - Article
C2 - 19124512
AN - SCOPUS:58349085991
SN - 1055-9965
VL - 18
SP - 297
EP - 305
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -