title: Impact of alcohol dehydrogenase gene 4 polymorphisms on esophageal squamous cell carcinoma risk in a Chinese population.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) is very common in China and is also one of the most common cancers worldwide. The purpose of this study was to examine the associations between genetic variants of various cancer-related genes and the risk of ESCC.
  
  
  METHODS
  In this study, we first examined the association between 18 potentially disruptive genetic variants of 17 genes, including alcohol dehydrogenase 4 (ADH4) and checkpoint kinase 2 (CHEK2), and ESCC risk in a Hangzhou population of 617 patients matched with 534 controls. Among the 18 single nucleotide polymorphisms (SNPs), two were validated in a Jinan population of 540 patients matched with 550 controls.
  
  
  RESULTS
  Sixteen SNPs in 15 genes, including CHEK2, did not have significantly different allele frequency distributions between ESCC patients and control subjects. A significantly increased risk of developing ESCC was revealed in subjects with the AA genotype of rs3805322 (ADH4) compared with those with the AG or GG genotype by unconditional univariate logistic regression analysis. Using a dominant model, the CC genotype of rs4822983 (CHEK2) had a marginally significant protective effect compared to the CT and TT genotypes. The association of ESCC risk with these two SNPs (rs3805322 and rs4822983) was further validated in a Jinan case-control set. Individuals with the ADH4 rs3805322 AA or AG genotype had ORs of 1.10 (95% CI = 0.81-1.49, P < 0.001) or 1.86 (95% CI = 1.33-2.59, P = 0.559), respectively, for developing ESCC compared with individuals with the GG genotype. CHEK2 rs4822983 CC carriers showed a marginally significantly decreased ESCC risk compared with those carrying the CT and TT genotypes in the validation set (95% CI = 0.61-1.01, P = 0.064). However, no evidence of interaction existed between the two SNPs and smoking or drinking in the Jinan case-control set.
  
  
  CONCLUSIONS
  In conclusion, this current study provides substantial evidence that genetic polymorphisms of rs3805322 in the ADH4 gene may be associated with an increased risk of developing ESCC in two Chinese Han populations. Future studies to address the biological function of this polymorphism in the development of ESCC are warranted.
authors.affiliation: Cancer Research Institute, Hangzhou, Zhejiang Province, China; Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Province, China; Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou City, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xu
authors.affiliation: Cancer Research Institute, Hangzhou, Zhejiang Province, China; Thoracic Surgery Department, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radio-Chemotherapy Oncology, Lishui People's Hospital, The Sixth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Shuang-Mei
authors.initials: SM
authors.lastname: Zhu
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou City, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Cancer Research Institute, Hangzhou, Zhejiang Province, China; Thoracic Surgery Department, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China; Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Province, China.
authors.forename: An
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou City, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Song
authors.affiliation: Cancer Research Institute, Hangzhou, Zhejiang Province, China; Thoracic Surgery Department, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China; Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Province, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Mao
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000235:genetics; D002681:China; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D009363:Neoplasm Proteins; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human