title: A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study.
abstract: BACKGROUND
  Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.
  
  
  METHODS
  To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.
  
  
  RESULTS
  In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14).
  
  
  CONCLUSIONS
  This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.
authors.affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, 363-951, Korea.
authors.forename: Hyung-cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyuna
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authors.lastname: Sung
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.forename: Kyoung-Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Young Jin
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authors.lastname: Kim
authors.forename: Min Jin
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authors.forename: Lian
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authors.forename: Yoon Shin
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authors.lastname: Cho
authors.forename: Miey
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authors.lastname: Park
authors.forename: Dong-Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Oh
authors.forename: Jun-Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Jae-Pil
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authors.lastname: Jeon
authors.forename: Soon-Young
authors.initials: SY
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authors.forename: Haesook
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authors.lastname: Min
authors.forename: Hyo Mi
authors.initials: HM
authors.lastname: Kim
authors.forename: Jaekyung
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authors.lastname: Park
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Min Hyuk
authors.initials: MH
authors.lastname: Lee
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Byeong-Woo
authors.initials: BW
authors.lastname: Park
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Kim
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Sang-Ah
authors.initials: SA
authors.lastname: Lee
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
authors.forename: Pei-Ei
authors.initials: PE
authors.lastname: Wu
authors.forename: Chia-Ni
authors.initials: CN
authors.lastname: Hsiung
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Hyung-Lae
authors.initials: HL
authors.lastname: Kim
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
mesh_terms: D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D066247:Receptor, ErbB-4; D015203:Reproducibility of Results; D056910:Republic of Korea
chemical_list: C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4