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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.

ABSTRACT: 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.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.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.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.

SUBMITTER: Yao S

PROVIDER: S-EPMC3446393 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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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 Song S Zirpoli Gary G Bovbjerg Dana H DH Jandorf Lina L Hong Chi Chen CC Zhao Hua H Sucheston Lara E LE Tang Li L Roberts Michelle M Ciupak Gregory G Davis Warren W Hwang Helena H Johnson Candace S CS Trump Donald L DL McCann Susan E SE Ademuyiwa Foluso F Pawlish Karen S KS Bandera Elisa V EV Ambrosone Christine B CB

Breast cancer research : BCR 20120404 2

<h4>Introduction</h4>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.<h4>Methods</h4>In a case (n = 928)-control (n = 843) study of breast cance ...[more]

PMID: 22480149

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Project description:INTRODUCTION:African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. METHODS:Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. RESULTS:Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. CONCLUSION:Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.

Dataset Information

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.

Publications

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.

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