Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk. / Northwood, Emma L.; Elliott, Faye; Forman, David; Barrett, Jennifer H.; Wilkie, Murray J. V.; Carey, Francis A.; Steele, Robert J. C.; Wolf, Roland; Bishop, Timothy; Smith, Gillian.
In: Pharmacogenetics and Genomics, Vol. 20, No. 5, 05.2010, p. 315-326.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk
A1 - Northwood,Emma L.
A1 - Elliott,Faye
A1 - Forman,David
A1 - Barrett,Jennifer H.
A1 - Wilkie,Murray J. V.
A1 - Carey,Francis A.
A1 - Steele,Robert J. C.
A1 - Wolf,Roland
A1 - Bishop,Timothy
A1 - Smith,Gillian
AU - Northwood,Emma L.
AU - Elliott,Faye
AU - Forman,David
AU - Barrett,Jennifer H.
AU - Wilkie,Murray J. V.
AU - Carey,Francis A.
AU - Steele,Robert J. C.
AU - Wolf,Roland
AU - Bishop,Timothy
AU - Smith,Gillian
PY - 2010/5
Y1 - 2010/5
N2 - <p>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.</p><p>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.</p><p>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).</p><p>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.</p>
AB - <p>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.</p><p>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.</p><p>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).</p><p>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.</p>
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 -