Objectives We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme.
Methods Nineteen polymorphisms in 13 genes [cytochrome P450 (P450), glutathione S-transferase (GST), N-acetyl transferase, quinone reductase (NQ01) and microsomal epoxide hydrolase (EPHX1) genes] were genotyped using multiplex PCR or Taqman-based allelic discrimination assays and analyzed in conjunction with diet, assessed by food frequency questionnaire, in a case-control study [317 CRA cases (308 cases genotyped), 296 controls]. Findings significant at a nominal 5% level are reported.
Results CRA risk was inversely associated with fruit (P = 0.02, test for trend) and vegetable (P = 0.001, test for trend) consumption. P450 CYP2C9*3 heterozygotes had reduced CRA risk compared with homozygotes for the reference allele [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.36-0.99], whereas CYP2D6*4 homozygotes (OR: 2.72; 95% CI: 1.18-6.27) and GSTM1 'null' individuals (OR: 1.43; 95% CI: 1.04-1.98) were at increased risk. The protective effect of fruit consumption was confined to GSTP1 (Ala(114)Val) reference allele homozygotes (OR: 0.49; 95% CI: 0.34-0.71, P = 0.03 for interaction). CRA risk was not associated with meat consumption, although a significant interaction between red meat consumption and EPHX1 (His(139)Arg) genotype was noted ( P = 0.02 for interaction).
Conclusion We report the novel associations between P450 genotype and CRA risk, and highlight the risk association with GSTM1 genotype, common to our CRA and cancer case-control series. In addition, we report a novel modifying influence of GSTP1 genotype on dietary chemoprevention. These novel findings require independent confirmation. Pharmacogenetics and Genomics 20: 315-326 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
AB -Objectives We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme.
Methods Nineteen polymorphisms in 13 genes [cytochrome P450 (P450), glutathione S-transferase (GST), N-acetyl transferase, quinone reductase (NQ01) and microsomal epoxide hydrolase (EPHX1) genes] were genotyped using multiplex PCR or Taqman-based allelic discrimination assays and analyzed in conjunction with diet, assessed by food frequency questionnaire, in a case-control study [317 CRA cases (308 cases genotyped), 296 controls]. Findings significant at a nominal 5% level are reported.
Results CRA risk was inversely associated with fruit (P = 0.02, test for trend) and vegetable (P = 0.001, test for trend) consumption. P450 CYP2C9*3 heterozygotes had reduced CRA risk compared with homozygotes for the reference allele [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.36-0.99], whereas CYP2D6*4 homozygotes (OR: 2.72; 95% CI: 1.18-6.27) and GSTM1 'null' individuals (OR: 1.43; 95% CI: 1.04-1.98) were at increased risk. The protective effect of fruit consumption was confined to GSTP1 (Ala(114)Val) reference allele homozygotes (OR: 0.49; 95% CI: 0.34-0.71, P = 0.03 for interaction). CRA risk was not associated with meat consumption, although a significant interaction between red meat consumption and EPHX1 (His(139)Arg) genotype was noted ( P = 0.02 for interaction).
Conclusion We report the novel associations between P450 genotype and CRA risk, and highlight the risk association with GSTM1 genotype, common to our CRA and cancer case-control series. In addition, we report a novel modifying influence of GSTP1 genotype on dietary chemoprevention. These novel findings require independent confirmation. Pharmacogenetics and Genomics 20: 315-326 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
KW - Colorectal adenoma KW - Diet KW - Gene-environment interactions KW - Pharmacogenetics KW - Polymorphism KW - Xenobiotic metabolizing enzymes KW - Glutathione-S-transferase KW - Epoxide hydrolase polymorphisms KW - Cytochrome P450 2D6 CYP2D6 KW - Meat consumption KW - Colon cancer KW - Cigarette smoking KW - Genetic polymorphisms KW - Vegetable consumption KW - Heterocyclic amines KW - GSTM1 genotypes U2 - 10.1097/FPC.0b013e3283395c6a DO - 10.1097/FPC.0b013e3283395c6a M1 - Article JO - Pharmacogenetics and Genomics JF - Pharmacogenetics and Genomics SN - 1744-6872 IS - 5 VL - 20 SP - 315 EP - 326 ER -