title: CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men.
abstract: OBJECTIVE
  To investigate the role of functional genetic polymorphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas.
  
  
  METHODS
  The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied were CYP1A1 2A (rs 4646903), CYP1A1 2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other lifestyle factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test.
  
  
  RESULTS
  None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1. A borderline significant interaction was observed for the combination of CYP1A1 2C and NQO1 (P = 0.051). The OR associated with CYP1A1 2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1 2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1 2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1 2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There was no measurable effect modification of smoking even regarding the combination of the genetic polymorphisms of the phase I and phase II enzymes.
  
  
  CONCLUSIONS
  Combination of the CYP1A1 2C and NQO1 609CC genotypes was associated with a decreased risk of colorectal adenomas regardless of smoking status.
authors.affiliation: Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Hamachi
authors.forename: Osamu
authors.initials: O
authors.lastname: Tajima
authors.forename: Kousaku
authors.initials: K
authors.lastname: Uezono
authors.forename: Shinji
authors.initials: S
authors.lastname: Tabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Abe
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008019:Life Style; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C413545:glutathione S-transferase T1
keywords: CYP1A1; Colorectal adenoma; GSTM1; GSTT1; NQO1; Polymorphism; Smoking