title: Association of CHRNA5-A3-B4 variation with esophageal squamous cell carcinoma risk and smoking behaviors in a Chinese population.
abstract: BACKGROUND
  CHRNA5-A3-B4, the gene cluster encoding nicotinic acetylcholine receptor subunits, is associated with lung cancer risk and smoking behaviors in people of European descent. Because cigarette smoking is also a major risk factor for esophageal squamous cell carcinoma (ESCC), we investigated the associations between variants in CHRNA5-A3-B4 and ESCC risk, as well as smoking behaviors, in a Chinese population.
  
  
  METHODS
  A case-control study of 866 ESCC patients and 952 healthy controls was performed to study the association of polymorphisms (rs667282 and rs3743073) in CHRNA5-A3-B4 with cancer risk using logistic regression models. The relationships between CHRNA5-A3-B4 polymorphisms and smoking behaviors that can be quantified by cigarettes smoked per day (CPD) and pack-years of smoking were separately estimated with Kruskal-Wallis tests among all 840 smokers.
  
  
  RESULTS
  CHRNA5-A3-B4 rs667282 TT/TG genotypes were associated with significantly increased risk of ESCC [adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.03 - 1.69, P = 0.029]. The increased ESCC risk was even higher among younger subjects (≤60 years) (OR = 1.44, 95% CI = 1.04 - 1.98, P = 0.024). These effects were not found in another polymorphism rs3743073. No evident association between the two polymorphisms and smoking behaviors was observed.
  
  
  CONCLUSIONS
  These results support the hypothesis that CHRNA5-A3-B4 is a susceptibility gene cluster for ESCC. The relationship between CHRNA5-A3-B4 and smoking behaviors in a Chinese population needs further investigation.
authors.affiliation: Department of Radiation, Oncology Center, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Haijian
authors.initials: H
authors.lastname: Wu
authors.forename: Qiji
authors.initials: Q
authors.lastname: Liu
authors.forename: Cuihong
authors.initials: C
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhu
authors.forename: Weijiang
authors.initials: W
authors.lastname: Fu
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Lv
authors.forename: Shikun
authors.initials: S
authors.lastname: Wang
authors.forename: Likuan
authors.initials: L
authors.lastname: Hu
mesh_terms: D000368:Aged; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012306:Risk; D012907:Smoking / Q000009:adverse effects*
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human