title: Gene-gene and gene-environment interactions between alcohol drinking habit and polymorphisms in alcohol-metabolizing enzyme genes and the risk of head and neck cancer in Japan.
abstract: Alcohol consumption is a strong risk factor for squamous cell carcinoma of the head and neck (SCCHN). The genetic polymorphisms aldehyde dehydrogenase2 (ALDH2) Glu487Lys and alcohol dehydrogenase 2 (ADH2) His47Arg, which have a strong impact on alcohol metabolism, are common in the Japanese population. To clarify the significance of these polymorphisms in SCCHN carcinogenesis, we conducted a matched case-control study with 239 incident SCCHN subjects and 716 non-cancer controls. Both ADH2 Arg/Arg and ALDH2 Glu/Lys were found to be independently associated with increased risk, with odds ratios (OR) of 2.67 (95% confidence interval [CI] 1.51-4.57) and 1.66 (95% CI 1.20-2.31), respectively. Further, compared with subjects having both ADH2 His/His and ALDH2 Glu/Glu, the adjusted OR and its 95% CI for those with both ADH2 Arg/Arg and ALDH2 Glu/Lys was 5.00 (2.32-10.71) in all subjects. This combination effect was evident in heavy drinkers (OR 11.3, 95% CI 2.97-43.3) but not in moderate or non-drinkers. Statistically significant gene-environment interactions between the two polymorphisms and drinking level were seen (ADH2 P = 0.035, ALDH2, P = 0.013). Furthermore, we also found a statistically significant gene-gene interaction between the two polymorphisms (P = 0.042). In conclusion, this case-control study showed a significantly increased risk of SCCHN in subjects with the ADH2 Arg/Arg and ALDH2 Glu/Lys polymorphisms in a Japanese population. In addition, our results also demonstrated that this risk was associated with significant gene-gene interactions between ADH2 and ALDH2 polymorphisms, as well as gene-environment interactions between these polymorphisms and alcohol drinking.
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan. ahiraki@aichi-cc.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics; D000437:Alcoholism / Q000453:epidemiology* / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D019943:Amino Acid Substitution; D001120:Arginine; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D004777:Environment; D005796:Genes; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D006639:Histidine; D006801:Humans; D007564:Japan / Q000453:epidemiology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D006639:Histidine; D001120:Arginine; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial