title: 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium.
abstract: BACKGROUND
  Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).
  
  
  METHODS
  To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls).
  
  
  RESULTS
  This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10(-29)] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (P(het)) = 1.3 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 0.43). rs865686 was associated with estrogen receptor-positive (ER(+)) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10(-22)) but less strongly, if at all, with ER-negative (ER(-)) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; P(het) = 1.16 × 10(-6)), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER(+) tumors.
  
  
  CONCLUSIONS
  This study is the first to show that rs865686 is a susceptibility marker for ER(+) breast cancer.
  
  
  CONCLUSIONS
  The findings further support the view that genetic susceptibility varies according to tumor subtype.
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom.
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mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone