title: Association between cancer risk and drug-metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in cases of lung cancer in Japan.
abstract: Genetic polymorphisms of enzymes involved in the metabolism of carcinogens are suggested to modify an individual's susceptibility to lung cancer. The purpose of this study was to investigate the relationship between lung cancer cases in Japan and variant alleles of cytochrome P450 (CYP) 2A6 (CYP2A6*4), CYP2A13 (CYP2A13*1-*10), CYP4B1 (CYP4B1*1-*7), sulfotransferase 1A1 (SULT1A1*2), glutathione S-transferase M1 (GSTM1 null), and glutathione S-transferase T1 (GSTT1 null). We investigated the distribution of these polymorphisms in 192 lung cancer patients and in 203 age- and sex-matched cancer-free controls. The polymorphisms were analyzed using various techniques including allele-specific PCR, hybridization probe assay, multiplex PCR, denaturing high-performance liquid chromatography (DHPLC), and direct sequencing. We also investigated allele and genotype frequencies and their association with lung cancer risk, demographic factors, and smoking status. The prevalence of the CYP2A6*4/*4 genotype in lung cancer cases was 3.6%, compared with 9.4% in the controls (adjusted OR = 0.36, 95% CI = 0.15-0.88, P = 0.025). In contrast, there was no association between the known CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1 polymorphisms and lung cancer. These data indicate that CYP2A6 deletions may be associated with lung cancer in the Japanese population studied.
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Honda
authors.forename: Yuka
authors.initials: Y
authors.lastname: Muroi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kanno
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
mesh_terms: D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015239:Arylsulfotransferase / Q000235:genetics; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D015239:Arylsulfotransferase; D065637:Cytochrome P-450 CYP2A6; D005982:Glutathione Transferase; C414206:CYP2A13 protein, human; C585710:CYP2A6 protein, human; C095029:cytochrome P-450 CYP4B1; C413545:glutathione S-transferase T1; C117544:SULT1A1 protein, human