Metabolic genotypes and risk for colorectal cancer.
BACKGROUND
Inherited polymorphisms that influence carcinogen metabolism or the composition of bile may influence the risk for the development of colorectal cancer.


METHODS
The frequency of polymorphisms involving N-acetyltransferase 1 (NAT1), NAT2, cytochrome P450 1A1 (CYP1A1), CYP2D6, CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and apolipoprotein E were compared in 219 white adults with sporadic colorectal cancer and 200 white controls attending for blood donation at a blood bank. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) after amplification of genomic DNA by polymerase chain reaction (PCR). Data were analyzed by using standard statistical methods for a case- control study, and reported as odds ratios (OR) with 95% confidence intervals (CI).


RESULTS
None of the genotypes, either alone or in combination, showed a strong association with colorectal cancer. Inheritance of the GSTT1 null genotype conferred a twofold risk of cancer that was statistically significant with crude data (OR 2.18; 95% CI 1.38-3.43), but not after adjustment for age (OR 1.91; 95% CI 0.99-3.70). There was also a trend towards a lower risk for proximal (right-sided) cancers in patients with apolipoprotein epsilon4 (OR 0.64; 95% CI 0.31-1.33).


CONCLUSIONS
No strong associations have been found between metabolic genotypes and colorectal cancer risk in Australia. Large studies will be required to confirm weak associations and to establish relationships between cancer risk, metabolic genotypes and exposure to dietary or other environmental carcinogens.
Butler
W J
WJ
Department of Gastroenterology, The Queen Elizabeth Hospital, The University of Adelaide, South Australia, Australia.
Ryan
P
P
Roberts-Thomson
I C
IC
D000123:Acetyltransferases / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors
D001057:Apolipoproteins E; D019389:Cytochrome P-450 CYP2D6; D000123:Acetyltransferases; D005982:Glutathione Transferase