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Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: A case-control study

Yao, S and Zirpoli, G and Bovbjerg, DH and Jandorf, L and Hong, CC and Zhao, H and Sucheston, LE and Tang, L and Roberts, M and Ciupak, G and Davis, W and Hwang, H and Johnson, CS and Trump, DL and McCann, SE and Ademuyiwa, F and Pawlish, KS and Bandera, EV and Ambrosone, CB (2012) Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: A case-control study. Breast Cancer Research, 14 (2). ISSN 1465-5411

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Abstract

Introduction: American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics.Methods: In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status.Results: More AAs had severe vitamin D deficiency (< 10 ng/ml) than EAs (34.3% vs 5.9%), with lowest levels among those with the highest African ancestry. Associations for SNPs differed by race. Among AAs, VDR SNP rs2239186, associated with higher serum levels of 25OHD, decreased risk after correction for multiple testing (OR = 0.53, 95% CI = 0.31-0.79, p by permutation = 0.03), but had no effect in EAs. The majority of associations were for ER-negative breast cancer, with seven differential associations between AA and EA women for CYP24A1 (p for interaction < 0.10). SNP rs27622941 was associated with a > twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs.Conclusions: These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women. © 2012 Yao et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yao, S
Zirpoli, G
Bovbjerg, DHdhb15@pitt.eduDHB15
Jandorf, L
Hong, CC
Zhao, H
Sucheston, LE
Tang, L
Roberts, M
Ciupak, G
Davis, W
Hwang, H
Johnson, CS
Trump, DL
McCann, SE
Ademuyiwa, F
Pawlish, KS
Bandera, EV
Ambrosone, CB
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 4 April 2012
Date Type: Publication
Journal or Publication Title: Breast Cancer Research
Volume: 14
Number: 2
DOI or Unique Handle: 10.1186/bcr3162
Refereed: Yes
ISSN: 1465-5411
Date Deposited: 20 Oct 2016 18:27
Last Modified: 02 Mar 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/29933

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