title: CYP1A1, GSTM1 and GSTT1 genetic polymorphisms and gastric cancer risk among Japanese: A nested case-control study within a large-scale population-based prospective study.
abstract: Cytochrome P450 (CYP) 1A1 and glutathione S-transferases (GST) M1 and T1 are major enzymes in the carcinogen metabolizing pathway. We examined the association between single nucleotide polymorphisms (SNPs) of CYP1A1 (rs4646421, rs4646422 and rs1048943), GSTM1 and GSTT1 and gastric cancer risk in Japan. This is a nested case-control study (457 cases and 457 matched controls) of our population-based cohort involving 36,745 subjects who answered a baseline questionnaire and supplied blood samples. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression models. We found that CYP1A1 (rs4646422) variant allele was associated with a statistically significant increased risk of gastric cancer compared with the homozygous wild-type genotype (OR = 1.65; 95% CI = 1.17-2.32). GSTM1 null, GSTT1 null and GSTM1/T1 both or either null genotypes were associated with increased risk, but not statistically significantly. Combination of the CYP1A1 (rs4646422) variant allele and GSTM1/T1 both or either null genotypes was associated with a statistically significant increased risk compared with the combination of the CYP1A1 homozygous wild-type genotype and the GSTM1/T1 both active genotypes. In addition, compared with CYP1A1 (rs4646422) homozygous wild-type genotypes in those who were never-smokers, CYP1A1 variant alleles in those who smoked ≥30 pack-years were associated with an increased risk; neither gene-gene nor gene-environment interactions were significant. The CYP1A1 (rs4646422) polymorphism might be involved in gastric carcinogenesis among the Japanese population.
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hidaka
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Sasazuki
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Aichi, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Hadrien
authors.initials: H
authors.lastname: Charvat
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Norie
authors.initials: N
authors.lastname: Sawada
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Shimazu
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Yamaji
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.|Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012042:Registries; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1
keywords: cytochrome P450 (CYP); gastric cancer; genetic polymorphism; glutathione S-transferase (GST); prospective study