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
Year: 2012
Type: article
Study design: Observational Study
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.
Source: Breast Cancer Research
DOI: 10.1186/bcr3162
Authors: 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
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: U.S. Department of Defense, Breast Cancer Research Foundation, Roswell Park Cancer Institute, State of New Jersey Department of Health, Memorial Sloan-Kettering Cancer Center, National Institutes of Health, Centers for Disease Control and Prevention, National Cancer Institute, National Center for Chronic Disease Prevention and Health Promotion
Awards: G1010591873, G131547209, G215985982, G2538813835, G2792577834, Obesity in ovarian cancer prognosis, G299563851, G3207950319, G3489946217, G4119534169, G4914835, G5446091787, Race & Risk Factors for Early/Aggressive Breast Cancer, Epidemiology of Breast Cancer Subtypes in African American Women: a Consortium, G7646998162, G8148863806, GENETIC FACTORS IN BREAST CANCER: CENTER FOR INTERDISCIPLINARY BEHAVIORAL RESEARCH, G8975859168
OpenAlex ID: W1983620628