RGD Reference Report - Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk. - Rat Genome Database

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Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk.

Authors: Northwood, EL  Elliott, F  Forman, D  Barrett, JH  Wilkie, MJ  Carey, FA  Steele, RJ  Wolf, R  Bishop, T  Smith, G 
Citation: Northwood EL, etal., Pharmacogenet Genomics. 2010 May;20(5):315-26. doi: 10.1097/FPC.0b013e3283395c6a.
RGD ID: 7495820
Pubmed: PMID:20375710   (View Abstract at PubMed)
DOI: DOI:10.1097/FPC.0b013e3283395c6a   (Journal Full-text)

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 (Ala114Val) 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 (His139Arg) 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colorectal adenoma susceptibilityIAGP 7495820DNA:deletion:cds (human)RGD 
colorectal adenoma  IAGP 7495820DNA:SNP: :p.A114V (human)RGD 
colorectal adenoma susceptibilityISOGSTM1 (Homo sapiens)7495820; 7495820DNA:deletion:cds (human)RGD 
colorectal adenoma  ISOGSTP1 (Homo sapiens)7495820; 7495820DNA:SNP: :p.A114V (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Gastrointestinal carcinoma  IAGP 7495820DNA:deletion:cdsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Gstm1  (glutathione S-transferase mu 1)
Gstp1  (glutathione S-transferase pi 1)

Genes (Mus musculus)
Gstm1  (glutathione S-transferase, mu 1)
Gstp1  (glutathione S-transferase, pi 1)

Genes (Homo sapiens)
GSTM1  (glutathione S-transferase mu 1)
GSTP1  (glutathione S-transferase pi 1)

Objects referenced in this article
Gene Gstm2 glutathione S-transferase, mu 2 Mus musculus
Gene Gstm2 glutathione S-transferase mu 2 Rattus norvegicus

Additional Information