title: Impact of smoking on lung cancer risk is stronger in those with the homozygous aldehyde dehydrogenase 2 null allele in a Japanese population.
abstract: The main lifestyle contributor to acetaldehyde exposure is the drinking of alcoholic beverages, but tobacco smoke also makes some contribution. Although acetaldehyde is associated with upper aerodigestive tract cancer risk, in accordance with genetically determined acetaldehyde metabolism, it is unclear whether lung cancer, a representative smoking-related cancer, is associated with acetaldehyde or genes impacting its metabolism. We conducted a case-control study to examine possible interaction between smoking and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism (rs671) on the risk of lung cancer in Japanese. Subjects were 718 lung cancer cases and 1416 non-cancer controls enrolled in the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Lifestyle factors, including smoking, were determined by self-administered questionnaire. We applied pack-years (PY; categorized into five levels: never, <15, <30, <45 and > or =45) as a marker of cumulative exposure to smoking. The impact of smoking, ALDH2 genotype, and their interaction on lung cancer risk were assessed by odds ratio (OR) and 95% confidence interval adjusted for potential confounders. Adjusted ORs for PY <15, <30, <45 and > or =45 relative to never smokers among those with Glu/Glu or Glu/Lys were 1.39, 1.80, 3.44 and 6.25, respectively (P-trend = 1.4 x 10(-30)). In contrast, ORs among Lys/Lys were 1.01, 10.2, 11.4 and 23.2, respectively (P-trend = 2.6 x 10(-7)). Interaction between ALDH2 genotype (Glu/Glu + Glu/Lys versus Lys/Lys) and cumulative smoking dose was statistically significant (P = 0.036) and was consistently observed in the analysis among never-drinkers (interaction P = 0.041). These results suggest that ALDH2 Lys/Lys, a null enzyme activity genotype, modifies the impact of smoking on the risk of lung cancer.
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8618, Japan.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Takakazu
authors.initials: T
authors.lastname: Kawase
authors.forename: Miki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takezaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects*
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial