Microsomal epoxide hydrolase gene polymorphism and susceptibility to coloncancer

We examined polymorphisms in exons 3 and 4 of microsomal epoxide hydrolase in 101 patients with colon cancer and compared the results with 203 control samples. The frequency of the exon 3 T to C mutation was higher in cancer patients than in controls (odds ratio 3.8; 95% confidence intervals 1.8-8.0 ). This sequence alteration changes tyrosine residue 113 to histidine and i s associated with lower enzyme activity when expressed in vitro. This sugge sts that putative slow epoxide hydrolase activity may be a risk factor for colon cancer. This appears to be true for both right- and left-sided tumour s, but was more apparent for tumours arising distally (odds ratio 4.1; 95% confidence limits 1.9-9.2). By contrast, there was no difference in prevale nce of exon 4 A to G transition mutation in cancer vs controls. This mutati on changes histidine residue 139 to arginine and produces increased enzyme activity. There was no association between epoxide hydrolase genotype and a bnormalities of p53 or Ki-Ras.