Vitamin D receptor polymorphisms and breast cancer risk

Results from the national cancer institute breast and prostate cancer cohort consortium

James D. McKay, Marjorie L. McCullough, Regina G. Ziegler, Peter Kraft, Barbara S. Saltzman, Elio Riboli, Aurelio Barricarte, Christine D. Berg, Goran Bergland, Sheila Bingham, Magritt Brustad, H. Bas Bueno-de-Mesquita, Laurie Burdette, Julie Buring, Eugenia E. Calle, Stephen J. Chanock, Françoise Clavel-Chapelon, David G. Cox, Laure Dossus, Heather Spencer Feigelson & 19 others Christopher A. Haiman, Susan E. Hankinson, Robert N. Hoover, David J. Hunter, Anika Husing, Rudolph Kaaks, Laurence N. Kolonel, Loic Le Marchand, Jakob Linseisen, Catherine A. McCarty, Kim Overvad, Salvatore Panico, Mark P. Purdue, Daniel O. Stram, Victoria L. Stevens, Dimitrios Trichopoulos, Walter C. Willett, Jeffrey Yuenger, Michael J. Thun

Research output: Contribution to journalArticle

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), 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 (US)
Pages (from-to)297-305
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

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Calcitriol Receptors
National Cancer Institute (U.S.)
Prostatic Neoplasms
Breast Neoplasms
Odds Ratio
Single Nucleotide Polymorphism
Genotype
Confidence Intervals
Vitamin D
Linkage Disequilibrium
RNA Stability
3' Untranslated Regions
Protein Isoforms
Biomarkers
Logistic Models
Cell Proliferation
Prospective Studies

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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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.; Bergland, Goran; Bingham, Sheila; Brustad, Magritt; Bueno-de-Mesquita, H. Bas; Burdette, Laurie; Buring, Julie; Calle, Eugenia E.; Chanock, Stephen J.; Clavel-Chapelon, Françoise; Cox, David G.; Dossus, Laure; Feigelson, Heather Spencer; Haiman, Christopher A.; Hankinson, Susan E.; Hoover, Robert N.; Hunter, David J.; Husing, Anika; Kaaks, Rudolph; Kolonel, Laurence N.; Le Marchand, Loic; Linseisen, Jakob; McCarty, Catherine A.; Overvad, Kim; Panico, Salvatore; Purdue, Mark P.; Stram, Daniel O.; Stevens, Victoria L.; Trichopoulos, Dimitrios; Willett, Walter C.; Yuenger, Jeffrey; Thun, Michael J.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 18, No. 1, 01.2009, p. 297-305.

Research output: Contribution to journalArticle

McKay, JD, McCullough, ML, Ziegler, RG, Kraft, P, Saltzman, BS, Riboli, E, Barricarte, A, Berg, CD, Bergland, G, Bingham, S, Brustad, M, Bueno-de-Mesquita, HB, Burdette, L, Buring, J, Calle, EE, Chanock, SJ, Clavel-Chapelon, F, Cox, DG, Dossus, L, Feigelson, HS, Haiman, CA, Hankinson, SE, Hoover, RN, Hunter, DJ, Husing, A, Kaaks, R, Kolonel, LN, Le Marchand, L, Linseisen, J, McCarty, CA, Overvad, K, Panico, S, Purdue, MP, Stram, DO, Stevens, VL, Trichopoulos, D, Willett, WC, Yuenger, J & Thun, MJ 2009, 'Vitamin D receptor polymorphisms and breast cancer risk: Results from the national cancer institute breast and prostate cancer cohort consortium', Cancer Epidemiology Biomarkers and Prevention, vol. 18, no. 1, pp. 297-305. https://doi.org/10.1158/1055-9965.EPI-08-0539
McKay, James D. ; McCullough, Marjorie L. ; Ziegler, Regina G. ; Kraft, Peter ; Saltzman, Barbara S. ; Riboli, Elio ; Barricarte, Aurelio ; Berg, Christine D. ; Bergland, Goran ; Bingham, Sheila ; Brustad, Magritt ; Bueno-de-Mesquita, H. Bas ; Burdette, Laurie ; Buring, Julie ; Calle, Eugenia E. ; Chanock, Stephen J. ; Clavel-Chapelon, Françoise ; Cox, David G. ; Dossus, Laure ; Feigelson, Heather Spencer ; Haiman, Christopher A. ; Hankinson, Susan E. ; Hoover, Robert N. ; Hunter, David J. ; Husing, Anika ; Kaaks, Rudolph ; Kolonel, Laurence N. ; Le Marchand, Loic ; Linseisen, Jakob ; McCarty, Catherine A. ; Overvad, Kim ; Panico, Salvatore ; Purdue, Mark P. ; Stram, Daniel O. ; Stevens, Victoria L. ; Trichopoulos, Dimitrios ; Willett, Walter C. ; Yuenger, Jeffrey ; Thun, Michael J. / Vitamin D receptor polymorphisms and breast cancer risk : Results from the national cancer institute breast and prostate cancer cohort consortium. In: Cancer Epidemiology Biomarkers and Prevention. 2009 ; Vol. 18, No. 1. pp. 297-305.
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title = "Vitamin D receptor polymorphisms and breast cancer risk: Results from the national cancer institute breast and prostate cancer cohort consortium",
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), 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.",
author = "McKay, {James D.} and McCullough, {Marjorie L.} and Ziegler, {Regina G.} and Peter Kraft and Saltzman, {Barbara S.} and Elio Riboli and Aurelio Barricarte and Berg, {Christine D.} and Goran Bergland and Sheila Bingham and Magritt Brustad and Bueno-de-Mesquita, {H. Bas} and Laurie Burdette and Julie Buring and Calle, {Eugenia E.} and Chanock, {Stephen J.} and Fran{\cc}oise Clavel-Chapelon and Cox, {David G.} and Laure Dossus and Feigelson, {Heather Spencer} and Haiman, {Christopher A.} and Hankinson, {Susan E.} and Hoover, {Robert N.} and Hunter, {David J.} and Anika Husing and Rudolph Kaaks and Kolonel, {Laurence N.} and {Le Marchand}, Loic and Jakob Linseisen and McCarty, {Catherine A.} and Kim Overvad and Salvatore Panico and Purdue, {Mark P.} and Stram, {Daniel O.} and Stevens, {Victoria L.} and Dimitrios Trichopoulos and Willett, {Walter C.} and Jeffrey Yuenger and Thun, {Michael J.}",
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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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EP - 305

JO - Cancer Epidemiology Biomarkers and Prevention

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