title: Association of CYP1A1, CYP1A2, GSTM1 and NAT2 gene polymorphisms with colorectal cancer and smoking.
abstract: We investigated CYP1A1*2A, CYP1A1*2C, CYP1A2*1C, CYP1A2*1F, GSTM1 and NAT2 gene polymorphisms, involving enzymes which metabolize many carcinogens, with reference to colorectal cancer risk. The distribution of these genotypes was not associated with risk overall. However, the CYP1A1*2A T/C genotype showed a significant association with colorectal cancer risk in never-smokers (odds ratio [OR], 3.06; 95% confidence interval [95% CI], 1.11-8.40; p = 0.030). The risk of the NAT2 rapid genotype in never-smokers was also statistically significantly increased (OR, 5.38; 95%CI, 1.80-16.1; p = 0.003). Furthermore, the joint effects of NAT2 rapid plus other genotypes were associated with colorectal cancer overall (OR, 3.12; 95%CI, 1.15-8.51; p = 0.026, for NAT2 rapid plus combined CYP1A1*2C Ile/Val and Val/Val, OR, 3.25; 95%CI, 1.09-9.74; p = 0.035, for NAT2 rapid plus CYP1A2*1C G/G, and OR, 4.20; 95%CI, 1.09-16.1; p = 0.037, for NAT2 rapid plus GSTM1 null, respectively). In never-smokers, the joint effects of NAT2 rapid plus other genotypes were remarkable (OR, 15.9; 95%CI, 1.87-135.8; p = 0.011, for NAT2 rapid plus combined CYP1A1*2A T/C and C/C, OR, 5.71; 95%CI, 1.49-21.9; p = 0.011, for NAT2 rapid plus combined CYP1A1*2C Ile/Val and Val/Val, and OR, 9.14; 95%CI, 2.05-40.7; p = 0.004, for NAT2 rapid plus CYP1A2*1F A/A, respectively). The joint effect of CYP1A2*1F A/A plus CYP1A2*1C G/G genotypes was also increased in never-smokers (OR, 6.16; 95%CI, 1.26-30.1; p = 0.025). Our findings suggest that the CYP1A1*2A T/C and NAT2 rapid genotypes is associated with colorectal cancer susceptibility without smoking exposure. These results also indicate that the NAT2 in combination with CYP1A1*2C, CYP1A2*1C, or GSTM1 genotypes may strongly confer susceptibility to colorectal cancer. In particular, the combination of NAT2 plus CYP1A1*2A, CYP1A1*2C, or CYP1A2*1F genotypes, and that of CYP1A2*1F plus CYP1A2*1C genotype may define a group of persons who are genetically susceptible to colorectal cancer in never smokers.
authors.affiliation: Faculty of Health Sciences, Kobe University Graduate School of Medicine, 7-10-2 Tomogaoka, Sumaku, Kobe 654-0142, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kayo
authors.initials: K
authors.lastname: Osawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kasahara
authors.forename: Aiko
authors.initials: A
authors.lastname: Miyaishi
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Saori
authors.initials: S
authors.lastname: Hayamizu
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Osawa
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Tsutou
authors.forename: Yohiki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Etsuji
authors.initials: E
authors.lastname: Shimada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Juro
authors.initials: J
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking / Q000453:epidemiology
chemical_list: D001191:Arylamine N-Acetyltransferase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; C478900:NAT2 protein, human