title: Impact of alcohol consumption with polymorphisms in alcohol-metabolizing enzymes on pancreatic cancer risk in Japanese.
abstract: The putative impact of alcohol on pancreatic cancer (PC) risk remains controversial. Here, we conducted a case-control study in Japanese to assess the impact of alcohol in conjunction with polymorphisms in alcohol-metabolizing enzymes. Cases were 160 patients with pancreatic cancer at Aichi Cancer Center, Nagoya, Japan. Two control groups of 800 age- and sex-matched non-cancer subjects each were independently selected. The impact of alcohol and polymorphisms in aldehyde dehydrogenase 2 (ALDH2) Glu504Lys, alcohol dehydrogenase (ADH) 1B His48Arg, and ADH1C Arg272Gln on PC risk was examined with multivariate analysis adjusted for potential confounders to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results showed no independent impact of alcohol or genotype on PC risk except former drinking. To avoid reverse causation, former drinkers were excluded in further analyses. In the analysis of the combined effects of alcohol consumption and genotype, significant impact of alcohol was seen for those subjects with ALDH2 Lys+ allele, ADH1B His/His, or ADH1C Arg/Arg (trend P = 0.077, 0.003, or 0.020, respectively), each of which is associated with a high concentration or rapid production of acetaldehyde. Analysis of genotype combinations showed that ‘ever drinking’ with both ADH1B His/His and ALDH2 Lys + was the most potent risk factor for PC relative to ‘never drinkers’ with both ADH1B His/His and ALDH2 Glu/Glu [OR (95% CI); 4.09 (1.30–12.85)]. These results indicate that alcohol has an impact on PC risk when the effects of alcohol consumption and metabolism are combined. Acetaldehyde may be involved in the mechanisms underlying PC development.
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Mizuno
authors.forename: Akira
authors.initials: A
authors.lastname: Sawaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamao
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000453:epidemiology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde