title: Pathway analyses identify TGFBR2 as potential breast cancer susceptibility gene: results from a consortium study among Asians.
abstract: BACKGROUND
  The TGF-β signaling pathway plays a significant role in the carcinogenic process of breast cancer.
  
  
  METHODS
  We systematically evaluated associations of common variants in TGF-β signaling pathway genes with breast cancer risk using a multistage, case-control study among Asian women.
  
  
  RESULTS
  In the first stage, 341 single-nucleotide polymorphisms with minor allele frequencies ≥ 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls recruited as a part of the Shanghai Breast Cancer Genetics Study (SBCGS). In the second stage, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls from the SBCGS. One variant, TGFBR2 rs1078985, had highly consistent and significant associations with breast cancer risk among participants in both study stages, as well as promising results from in silico analysis. Additional genotyping was carried out among 2,475 cases and 2,343 controls from the SBCGS, as well as among 5,077 cases and 5,384 controls from six studies in the Asian Breast Cancer Consortium (stage III). Pooled analysis of all data indicated that minor allele homozygotes (GG) of TGFBR2 rs1078985 had a 24% reduced risk of breast cancer compared with major allele carriers (AG or AA; OR, 0.76; 95% CI, 0.65-0.89; P = 8.42 × 10(-4)).
  
  
  CONCLUSIONS
  These findings support a role for common genetic variation in TGF-β signaling pathway genes, specifically in TGFBR2, in breast cancer susceptibility.
  
  
  CONCLUSIONS
  These findings may provide new insights into the etiology of breast cancer as well as future potential therapeutic targets.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Ma
authors.forename: Alicia
authors.initials: A
authors.lastname: Beeghly-Fadiel
authors.forename: Wei
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authors.lastname: Lu
authors.forename: Jiajun
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authors.lastname: Shi
authors.forename: Yong-Bing
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authors.lastname: Xiang
authors.forename: Qiuyin
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authors.lastname: Cai
authors.forename: Hongbing
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authors.lastname: Shen
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
authors.forename: Zefang
authors.initials: Z
authors.lastname: Ren
authors.forename: Keitaro
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authors.lastname: Matsuo
authors.forename: Ui Soon
authors.initials: US
authors.lastname: Khoo
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.forename: Ben
authors.initials: B
authors.lastname: Zhang
authors.forename: Bu-Tian
authors.initials: BT
authors.lastname: Ji
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Pei-Ei
authors.initials: PE
authors.lastname: Wu
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: Shieh
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kasuga
authors.forename: Kelvin Y K
authors.initials: KY
authors.lastname: Chan
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Harold L
authors.initials: HL
authors.lastname: Moses
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000328:Adult; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II