Colorectal cancer risk in relation to genetic polymorphism of cytochrome P450 1A1, 2E1, and glutathione-S-transferase M1 enzymes.
Chemical carcinogens generally require metabolic activation in order to be able to bind to DNA and contribute to cancer causation. Most of the human metabolizing enzymes are genetically polymorphic, and these polymorphisms may affect the enzyme activity or inducibility. In our present study we investigated the connection between genetic polymorphism of cytochrome P450 1A1, 2E1 (phase I enzymes) and glutathione-S-transferase M1 (a phase II enzyme) and colorectal cancer occurrence in a Hungarian population. The CYP 2E1 c2 allele proved to be in significant association with colorectal cancer (OR: 1.91, 95% CI: 1.05-3.52), the CYP 1A1 Val allele was also overrepresented among colon cancer patients (OR: 1.57, 95% CI: 0.90-2.74), and the frequency of GSTM1 homozygous 0 genotype showed only minor difference (OR: 1.19, 95% CI: 0.75-1.35). Combined analysis of the polymorphisms showed that individuals carrying all the three "high-risk" alleles have a strikingly increased risk for sporadic colorectal cancer (OR: 4.62, 95% CI: 1.23-25.68).
Kiss
I
I
Department of Preventive Medicine, University Medical School of Pécs, Hungary.
Sándor
J
J
Pajkos
G
G
Bogner
B
B
Hegedüs
G
G
Ember
I
I
D000230:Adenocarcinoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D000483:Alleles; D001711:Biotransformation / Q000235:genetics; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D006814:Hungary; D006841:Hydrocarbons, Aromatic / Q000493:pharmacokinetics; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009602:Nitrosamines / Q000493:pharmacokinetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012306:Risk; D044465:White People / Q000235:genetics
D002274:Carcinogens, Environmental; D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D006841:Hydrocarbons, Aromatic; D007527:Isoenzymes; D009602:Nitrosamines