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01.04.2012 | Research article | Ausgabe 2/2012 Open Access

Breast Cancer Research 2/2012

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

Zeitschrift:
Breast Cancer Research > Ausgabe 2/2012
Autoren:
Song Yao, Gary Zirpoli, Dana H Bovbjerg, Lina Jandorf, Chi Chen Hong, Hua Zhao, Lara E Sucheston, Li Tang, Michelle Roberts, Gregory Ciupak, Warren Davis, Helena Hwang, Candace S Johnson, Donald L Trump, Susan E McCann, Foluso Ademuyiwa, Karen S Pawlish, Elisa V Bandera, Christine B Ambrosone
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​bcr3162) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

SY helped to develop the hypothesis, design the study, and perform the data analysis and interpretation. CBA helped to develop the hypothesis, design the study, provide the data and biospecimen from the WCHS, perform the data analysis and interpretation, and provide financial support for the study. GZ helped to provide the data and biospecimen from the WCHS and to perform the data analysis and interpretation. DHB, LJ, MR, GC, WD, KSP, and EVB helped to provide the data and biospecimen from the WCHS. HH provided pathological data of tumor samples. C-CH, LES, LT, CSJ, DLT, SEM and FA helped to perform the data analysis and interpretation. HZ helped to provide financial support for the study. All authors read and approved the final draft of the manuscript.

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.
Zusatzmaterial
Additional file 1: Supplementary Tables S1-S5. The file contains the following five supplementary tables. Table S1. Breast cancer risk associated with SNPs in VDR, CYP27B1, and CYP24A1 in African American and European American women. Table S2. Haplotypes of VDR and CYP24A1 in significant association with breast cancer risk in African American and European American women. Table S3. Risk of estrogen receptor positive breast cancer associated with SNPs in VDR, CYP27B1, and CYP24A1 in African Americana and European American women. Table S4. Risk of estrogen receptor negative breast cancer associated with SNPs in VDR, CYP27B1, and CYP24A1 in African Americana and European American women. Table S5. SNPs in VDR that show differential associations with breast cancer stratified by menopausal status in African American and European American women. (DOC 704 KB)
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Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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