title: Common genetic variants associated with breast cancer in Korean women and differential susceptibility according to intrinsic subtype.
abstract: BACKGROUND
  Recently identified genetic variants from genome-wide association studies (GWAS) on breast cancer have not been validated in Asian populations, except in China. In this study, we sought to confirm the association between known variants and breast cancer in Korean women and further evaluate the associations of individual single nucleotide polymorphisms (SNP) with different intrinsic subtypes of breast cancer.
  
  
  METHODS
  In total, 3,321 invasive breast cancer patients and 3,500 healthy controls were genotyped for five SNPs by using the TaqMan assay. The SNPs genotyped included rs2046210 (6q25.1), rs2981582 (FGFR2), rs889312 (MAP3K1), rs3803662 (TOX3/TNRC9), and rs4973768 (SLC4A7). Tumors were classified into four intrinsic subtypes based on estrogen receptor (ER), progesterone receptor, HER2, and Ki67 expression.
  
  
  RESULTS
  All five SNPs were significantly associated with risk of breast cancer in dominant, recessive, and additive models. ORs per risk allele (95% CI) were 1.29 (1.16-1.43), 1.40 (1.18-1.68), 1.22 (1.06-1.41), 1.52 (1.30-1.77), and 1.20 (1.08-1.33) for rs2046210, rs2981582, rs889312, rs3803662, and rs4973768, respectively. A multigene logistic regression risk model was generated with the SNPs. In subtype analysis, all 5 SNPs were associated with the Luminal A subtype. Two SNPs (rs2046210 and rs3803662) were linked to the ER(-)HER2(+) subtype, and only rs2046210 SNP was associated with the triple-negative subtype.
  
  
  CONCLUSIONS
  The five SNPs from GWAS were significantly associated with breast cancer risk in Korean women. Associations were heterogeneous according to the intrinsic subtype of breast cancer.
  
  
  CONCLUSIONS
  Our result is an important contribution to the literature about genetic susceptibility for breast cancer in nonwhite populations.
authors.affiliation: Cancer Research Institute, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Woo
authors.forename: Jong-Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Lee
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000145:classification* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D007723:Korea / Q000453:epidemiology; D018895:Microsatellite Repeats; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human