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

Details

• Alternative Title:
  Breast Cancer Res
• Personal Author:
  Yao, Song ; Zirpoli, Gary ; Bovbjerg, Dana H ; Jandorf, Lina ; Hong, Chi Chen ; Zhao, Hua ; Sucheston, Lara E ; Tang, Li ; Roberts, Michelle ; Ciupak, Gregory ; Davis, Warren ; Hwang, Helena ; Johnson, Candace S ; Trump, Donald L ; McCann, Susan E ; Ademuyiwa, Foluso ; Pawlish, Karen S ; Bandera, Elisa V ; Ambrosone, Christine B
• Description:
  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.
  
  
• Subjects:
  Black Or African American Breast Neoplasms Case-Control Studies Female Humans Middle Aged Polymorphism, Single Nucleotide Receptors, Calcitriol Receptors, Estrogen Risk Factors Steroid Hydroxylases Vitamin D Vitamin D3 24-Hydroxylase Vitamin D Deficiency White

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• Source:
  Breast Cancer Res. 2012; 14(2):R58.
• Pubmed ID:
  22480149
• Pubmed Central ID:
  PMC3446393
• Document Type:
  Journal Article
• Funding:
  DP07-703/DP/NCCDPHP CDC HHS/United States ; K07 CA148888/CA/NCI NIH HHS/United States ; K22 CA138563/CA/NCI NIH HHS/United States ; N01-PC-95001-20/PC/NCI NIH HHS/United States ; P01 CA151135/CA/NCI NIH HHS/United States ; P30 CA016056-32/CA/NCI NIH HHS/United States ; R01 CA100598/CA/NCI NIH HHS/United States
• Volume:
  14
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f56c8c9d109bdddf9220b6d42d62e07fda7b89217f033c5c3f21993fffc4fa2f
• Download URL:
  https://stacks.cdc.gov/view/cdc/22710/cdc_22710_DS1.pdf
• File Type:
  [PDF - 912.16 KB ]