title: Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County.
abstract: BACKGROUND
  The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk.
  
  
  METHODS
  A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for CYP2E1 G1259C, hOGG1 C326G, MTHFR C677T, MPO G463A, and ALDH2 allele genes were identified in blood samples collected from all participants.
  
  
  RESULTS
  The alleles ALDH2 and MTHFR C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the ALDH 1*1 genotype, the ALDH 2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of MTHFR C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of ALDH 2 and TT/TC of MTHFR C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (ORG) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus.
  
  
  CONCLUSIONS
  The study demonstrated that the genotypes ALDH2*2 and MTHFR 677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Qing Da
authors.initials: QD
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Mei Shu
authors.initials: MS
authors.lastname: Wang
authors.forename: Tao Yu
authors.initials: TY
authors.lastname: Diao
authors.forename: Zhi Ying
authors.initials: ZY
authors.lastname: Zhou
authors.forename: Qiang Xue
authors.initials: QX
authors.lastname: Fang
authors.forename: Fang Yan
authors.initials: FY
authors.lastname: Yang
authors.forename: Qing Hui
authors.initials: QH
authors.lastname: Li
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D002681:China; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004945:Esophagoscopy; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D042965:Methylenetetrahydrofolate Reductase (NADPH2)