title: Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles.
abstract: BACKGROUND
  Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis.
  
  
  OBJECTIVE
  To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed.
  
  
  RESULTS
  Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10(-40) and OR=4.13, p=8.4×10(-76), respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk.
  
  
  CONCLUSIONS
  Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsurumaru
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kajiyama
authors.forename: Hoichi
authors.initials: H
authors.lastname: Kato
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Igaki
authors.forename: Koh
authors.initials: K
authors.lastname: Furuta
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Fujita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Setoyama
authors.forename: Shinkan
authors.initials: S
authors.lastname: Tokudome
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Haraguchi
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D016022:Case-Control Studies; D003043:Cocarcinogenesis; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology
chemical_list: D009363:Neoplasm Proteins; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial