title: 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: BACKGROUND
  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.
authors.affiliation: Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. song.yao@roswellpark.org
authors.forename: Song
authors.initials: S
authors.lastname: Yao
authors.forename: Gary
authors.initials: G
authors.lastname: Zirpoli
authors.forename: Dana H
authors.initials: DH
authors.lastname: Bovbjerg
authors.forename: Lina
authors.initials: L
authors.lastname: Jandorf
authors.forename: Chi Chen
authors.initials: CC
authors.lastname: Hong
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.forename: Lara E
authors.initials: LE
authors.lastname: Sucheston
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Michelle
authors.initials: M
authors.lastname: Roberts
authors.forename: Gregory
authors.initials: G
authors.lastname: Ciupak
authors.forename: Warren
authors.initials: W
authors.lastname: Davis
authors.forename: Helena
authors.initials: H
authors.lastname: Hwang
authors.forename: Candace S
authors.initials: CS
authors.lastname: Johnson
authors.forename: Donald L
authors.initials: DL
authors.lastname: Trump
authors.forename: Susan E
authors.initials: SE
authors.lastname: McCann
authors.forename: Foluso
authors.initials: F
authors.lastname: Ademuyiwa
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pawlish
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D001741:Black or African American / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood*; D014808:Vitamin D Deficiency / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase; D044465:White People / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase