title: CYP2A6 genetic polymorphism is associated with decreased susceptibility to squamous cell lung cancer in Japanese smokers.
abstract: Cytochrome P450 2A6 (CYP2A6) is an enzyme involved in the metabolism of tobacco carcinogens, which are important risk factors in lung cancer. We and others have previously reported that CYP2A6*4, a whole-gene deletion polymorphism, is associated with lower risk of lung cancer than the wild-type allele. However, the genotyping method used in these previous studies considered only the CYP2A6*4 allele; this lead to insufficient classification of the CYP2A6 genotype, thereby underestimating the frequencies of the deficient alleles. In this study, CYP2A6 genotypes of Japanese smokers (110 individuals with squamous cell lung cancer (SQCC) and 132 sex-matched cancer-free controls) were determined using a sequencing-based approach to determine CYP2A6 haplotypes. The risk of SQCC was evaluated using the activity score (AS) system to predict CYP2A6 phenotype from its genotype. The risk of developing SQCC was significantly lower in the poor metabolizers assigned as AS 0.5 (adjusted odds ratio [OR] = 0.13, 95% CI = 0.04-0.45, P = 0.001) and AS 0 (adjusted OR = 0.15, 95% CI = 0.03-0.82, P = 0.028) than in the extensive metabolizers assigned as AS 2.0. In conclusion, CYP2A6 genetic polymorphisms may play important roles in the development of SQCC in Japanese smokers.
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hosono
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kumondai
authors.affiliation: Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.affiliation: Department of Environmental and Health Science, Tohoku Pharmaceutical University, Sendai, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: mhira@m.tohoku.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D065637:Cytochrome P-450 CYP2A6 / Q000172:deficiency*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*
chemical_list: C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6
keywords: Activity score; CYP2A6; Genetic polymorphism; Smoker; Squamous cell lung cancer