A case-control study of microsomal epoxide hydrolase, smoking, meat consumption, glutathione S-transferase M3, and risk of colorectal adenomas.
We estimated associations between polymorphisms in the gene encoding microsomal epoxide hydrolase (mEH) among 464 cases diagnosed with first occurrence of colorectal adenoma and 510 matched controls. In an analysis controlling only for the matching variables, we found little or no association between adenoma and mEH genotypes defined by polymorphisms at either codon 113 and 139 or mEH activity predicted by both polymorphisms. However, in subsequent analyses, high predicted mEH activity was significantly associated with adenoma among certain subgroups defined by smoking history [odds ratio (OR), 4.27; 95% confidence interval (CI), 1.68-10.81 among current smokers; interaction, P = 0.11], meat consumption (OR, 2.47; CI, 0.99-6.19 among individuals who regularly eat well-done meat; interaction, P = 0.03), and genotypes for the *A/*B polymorphism in the gene encoding glutatione S-transferase M3 (OR, 2.60; CI, 1.28-5.28 among individuals with *A*A genotype; interaction, P = 0.03). These findings are consistent with causal roles for environmental polycyclic aromatic hydrocarbons and genetically encoded variants in enzymes whose actions lead to the production of activated polycyclic aromatic hydrocarbon metabolites.
Cortessis
V
V
Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles 90089, USA.
Siegmund
K
K
Chen
Q
Q
Zhou
N
N
Diep
A
A
Frankl
H
H
Lee
E
E
Zhu
Q S
QS
Haile
R
R
Levy
D
D
D000236:Adenoma / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D000368:Aged; D001711:Biotransformation; D002273:Carcinogens / Q000009:adverse effects* / Q000493:pharmacokinetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D004032:Diet; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008460:Meat / Q000009:adverse effects; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects* / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D002273:Carcinogens; D007527:Isoenzymes; D011084:Polycyclic Aromatic Hydrocarbons; D005982:Glutathione Transferase; C416969:glutathione transferase M3-3; D004851:Epoxide Hydrolases