title: Combination of ALDH2 and ADH1B polymorphisms is associated with smoking initiation: A large-scale cross-sectional study in a Japanese population.
abstract: Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms are known to strongly influence alcohol　drinking behavior. Given evidence of an association between smoking and drinking behaviors, we hypothesized that ALDH2/ADH1B polymorphisms might also be associated with smoking initiation, and conducted a cross-sectional study to examine this hypothesis.
  
  
  
  Study subjects were first-visit outpatients diagnosed not to have cancer at Aichi Cancer Center Hospital between 2001 and 2005, including 4141 never smokers and 2912 ever smokers. Unconditional logistic regression models were applied to estimate odds ratios (OR) and 95% confidence intervals (CI) for smoking initiation by comparing ever smokers with never smokers.
  
  
  
  Excessive alcohol drinking was associated with a higher likelihood of ever smoking. After adjustment for drinking behaviors, compared to individuals with ALDH2 Glu/Glu, the ORs of ever smoking were 1.71 (95% CI, 1.49-1.95) and 2.28 (1.81-2.87) among those with ALDH2 Glu/Lys and Lys/Lys, respectively. Combination of ALDH2 Lys/Lys and ADH1B His/His (i.e., the most alcohol-intolerant subpopulation) showed the highest OR [2.44 (1.84-3.23)], whereas combination of ALDH2 Glu/Glu and ADH1B Arg/Arg (i.e., the most alcohol-tolerant subpopulation) showed the lowest OR [0.83 (0.57-1.21)] compared with ALDH2 Glu/Glu and ADH1B His/His.
  
  
  
  Besides the amount and frequency of alcohol drinking, the combination of ALDH2 and ADH1B polymorphisms predicts smoking initiation. This study suggests that alcohol tolerance regulated by ALDH2 and ADH1B polymorphisms is associated with smoking initiation, and facilitates the development of targeted interventions to reduce smoking prevalence.
authors.affiliation: Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Masaoka
authors.affiliation: Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; Department of Epidemiology, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Via G. La Masa 19, 20156 Milan, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Gallus
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.affiliation: Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; Department of Epidemiology, Nagoya University Graduate School of Medicine, 65 Tsurumai Showa-ku, Nagoya 466-8550, Japan. Electronic address: kmatsuo@aichi-cc.jp.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: Alcohol drinking; Polymorphism; Smoking initiation