title: Genetic susceptibility loci for subtypes of breast cancer in an African American population.
abstract: BACKGROUND
  Most genome-wide association studies (GWAS) have been carried out in European ancestry populations; no risk variants for breast cancer have been identified solely from African ancestry GWAS data. Few GWAS hits have replicated in African ancestry populations.
  
  
  METHODS
  In a nested case-control study of breast cancer in the Black Women's Health Study (1,199 cases/1,948 controls), we evaluated index single-nucleotide polymorphisms (SNP) in 21 loci from GWAS of European or Asian ancestry populations, overall, in subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status (ER+/PR+, n = 336; ER-/PR-, n = 229), and in triple-negative breast cancer (TNBC, N = 81). To evaluate the contribution of genetic factors to population differences in breast cancer subtype, we also examined global percent African ancestry.
  
  
  RESULTS
  Index SNPs in five loci were replicated, including three associated with ER-/PR- breast cancer (TERT rs10069690 in 5p15.33, rs704010 in 10q22.3, and rs8170 in 19p13.11): per allele ORs were 1.29 [95% confidence interval (CI) 1.04-1.59], P = 0.02, 1.52 (95% CI 1.12-2.08), P = 0.01, and 1.30 (95% CI 1.01-1.68), P = 0.04, respectively. Stronger associations were observed for TNBC. Furthermore, cases in the highest quintile of percent African ancestry were three times more likely to have TNBC than ER+/PR+ cancer.
  
  
  CONCLUSIONS
  These findings provide the first confirmation of the TNBC SNP rs8170 in an African ancestry population, and independent confirmation of the TERT ER- SNP. Furthermore, the risk of developing ER- breast cancer, particularly TNBC, increased with increasing proportion of global African ancestry.
  
  
  CONCLUSIONS
  The findings illustrate the importance of genetic factors in the disproportionately high occurrence of TNBC in African American women.
authors.affiliation: Slone Epidemiology Center at Boston University, 1010 Commonwealth Avenue, Boston, MA 02215, USA. jpalmer@bu.edu
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ruiz-Narvaez
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Yvette C
authors.initials: YC
authors.lastname: Cozier
authors.forename: Lucile L
authors.initials: LL
authors.lastname: Adams-Campbell
authors.forename: Lynn
authors.initials: L
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human