The colon is subject to oxidative and free radical damage by both products of endogenous metabolism and bacterial fermentation within the gut lumen. These injurious stimuli may cause cell damage or cell death or even lead to mutations, resulting in tumour initiation and progression. Colon cancer is a common disease, with the highest incidence in developed countries. The aetiology is unknown, but in addition to diet and cigarette smoking (Giovannucci and Willett, 1994) there is a complex polygenic background that determines individual susceptibility to disease. There is currently much interest in the roles of oncogenes, tumoursuppressor genes and mismatch repair enzymes in colon cancer (Tomlinson et al, 1997). In addition, interindividual variation in the ability to dispose of reactive xenobiotics catalysed by glutathione S-transferases GST-M1 and GST-T1 has been investigated (Lang et al, 1986;Strange et al, 1991;Zhong et al, 1993;Chenevix-Trench et al, 1995). However, results from a number of studies show only weak and inconsistent associations with disease susceptibility. N-acetyltransferase 2 (NAT-2) polymorphism may be implicated in susceptibility to colon cancer (Lang et al, 1986;Wohlleb et al, 1990;Illett et al, 1994;Probst-Hensch et al, 1995), but there is evidence that its relationship may be by linkage with other genes rather than causally (Hubbard et al, 1997).We have used a polymerase chain reaction (PCR) strategy to investigate whether polymorphisms in the microsomal epoxide hydrolase gene (mEPHX) (Hassett et al, 1994) have any relationship to colon cancer. The enzyme is expressed in many tissues, including colon and liver. Polymorphisms of mEPHX may have functional significance. There is variation in exon 3, where a T to C alteration changes tyrosine residue 113 to histidine and is associated with lower enzyme activity when expressed in vitro. By contrast, A to G transition in exon 4 changes histidine residue 139 to arginine and produces increased enzyme activity. The effect of combining the alleles has not been established. The activity of mEPHX varies more than 50-fold in Caucasians (Omiecinski et al, 1993). This variation of activity is, thus, due to a combination of genetic polymorphism, transcriptional and post-transcriptional control of gene expression. MATERIALS AND METHODS Controls and cancer casesControl blood samples (n = 203) were obtained anonymously from the Scottish National Blood Transfusion Service. These were Caucasian individuals aged between 18 and 65 years with equal sex distribution. This group has been previously described (Cantlay et al, 1994) and was drawn from the same geographical area as the cancer study group. The presence of colorectal neoplasia was not specifically excluded, but all patients were healthy. Peripheral blood from patients with colorectal cancer was collected from a consecutive series of operable colorectal cancer cases after surgery in four local hospitals between 1988 and 1993 (n = 101). Cancer patient dataCancer diagnosis was confirmed histopathologically...

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Background-Genetic polymorphisms in N-acetyltransferase (NAT2) can change the normally fast acetylation of substrates to slow acetylation, and have been associated with the development of some cancers. The NAT2 locus may also suVer dysregulation during cancer progression, as the gene resides on chromosome 8p22, a region which is frequently deleted in colorectal cancer. Subjects and Methods-A polymerase chain reaction based method was used to determine NAT2 genotype in 275 patients with colon cancer and 343 normal control DNAs. Within the cancer group, 65 cases known to contain deletions in chromosome 8p were examined for loss of heterozygosity at the NAT2 locus. Results-Overall, there was no statistical diVerence in frequency or distribution of NAT2 alleles and genotype between colon cancer and control groups. There was a significant association between the slow acetylation genotype and early age of onset. NAT2 genotype did not vary with other clinical features of colon cancer, which included Dukes's stage, site of tumour, and sex. Of 48 informative cases, only three (6%) showed loss of heterozygosity, indicating that the NAT2 locus is not commonly deleted in colorectal cancer. This suggests that NAT2 is retained during the process of allele loss possibly because of its proximity to a gene necessary for cell viability. Conclusions-NAT2 does not play a major role in colorectal cancer risk, but may influence risk in some age groups. The nature of the loss of heterozygosity at the chromosome 8p site is complex and is worthy of further study. (Gut 1997; 41: 229-234)

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