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Glutathione S-transferase (GST) enzymes catalyse the detoxification of by-products of reactive oxygen species and are thus important in cellular defence mechanisms. The GSTs are polymorphic with allelic variants encoding isoforms with functional differences. GST polymorphism has been associated with susceptibility and clinical outcome in patients with cancer. In this retrospective cohort, we have investigated associations between common GSTM1, GSTM3 and GSTP1 polymorphisms with factors known to influence clinical outcome and patient survival in colorectal cancer. Significant linkage disequilibrium was demonstrated between GSTM1 and GSTM3 alleles (P≤0.001). We identified no significant associations between the GSTP1 Ile105Val105 polymorphism and any clinical outcome parameters or patient survival. However significant associations were demonstrated with mu class GSTs. Those patients who were GSTM1 null presented less frequently with poorly-differentiated tumours (P=0.038). Furthermore, patients who were GSTM3 AA were less likely to present with advanced stage tumours (T-stage, P=0.036 and Dukes' classifications, P=0.012) or distant metastases (P=0.017) when examined alone. Upon further examination of the effect of linkage disequilibrium, we found that, in GSTM1 null individuals, GSTM3 AA (compared with other GSTM3 genotypes combined) had longer disease-free survival (HR=0.54, 95% CI 0.30-0.98, P=0.044). Thus, the GSTM3 AA genotype is associated with improved prognosis especially in those with GSTM1 null. Our findings suggest that the GST mu gene cluster mediates tumour characteristics and survival in patients with colorectal cancer.

The recent introduction of restorative proctocolectomy for the treatment of ulcerative colitis has reopened the debate about the effects of ileostomy on quality of life. This study analysed life quality and psychological morbidity in 113 patients with an ileostomy using a postal questionnaire which included questions about their opinion of the pouch operation. Of the questionnaires, 73 per cent were suitable for analysis. A total of 93 per cent of those responding were happy with the ileostomy and appeared to have adapted to a normal life with it. Some 87 per cent stated that they would keep the ileostomy in preference to an ileoanal pouch. In addition, psychological morbidity as assessed by the General Health Questionnaire occurred in only 5 per cent of patients.

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Recent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p ‫؍‬ 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference Key words: chromosome 10q; LOH; sporadic colorectal adenocarcinoma; TSG; tumor progressionColorectal adenocarcinoma is the second most common cause of cancer related death in the Western world. The majority of colorectal cancers are considered sporadic and present in the 7th and 8th decades of life, whereas hereditary colorectal adenocarcinoma accounts for approximately 10% of all cases and usually presents before the age of 50 years. 1 The initiation and progression of sporadic colorectal tumors has been described as a multi-step etiology involving the progressive loss of tumour suppressor function and concomitant inappropriate oncogene activation resulting in the deregulation of controlled cellular proliferation. 2 Frequent loss of heterozygosity (LOH) has been shown in regions harboring known tumour suppressor genes including 5q21(APC), 17p13(p53) and 18q21(DCC) involved in the development of sporadic colorectal adenocarcinoma. 2 Studies have shown frequent LOH on chromosome 10q in several tumour types including malignant gliomas, 3 malignant melanomas, 4 prostate, 5,6 endometrial, 7 breast 8,9 and bladder cancer. 10 Early studies of this chromosome, however, showed infrequent loss in colorectal cancer. 11 A subsequent allelotyping study 12 of sporadic colorectal adenocarcinomas showed that LOH on chromosome 10q was an infrequent event, however, this study only investigated a single locus (10q25-26). More recently Frayling et al. 13 using a more centromeric marker (D10S220) showed frequent LOH (37%) in sporadic colorectal adenocarcinomas on 10q11-21 suggesting the presence of a tumour suppressor gene (TSG) in this region. The presence of a TSG in this region is supported by findings in other tumour types including renal, 14 chondrosarcomas 15 and malignant glioma 3 that have shown frequent LOH at 10q11-21.Recently a TSG called PTEN, MMAC1 or TEP1 16 -18 has been localized to the chromosomal loci 10q23.3, loss and concomitant mutation in the retained PTEN allele have been shown in glioblastomas, 19 malignant melanoma, 20,21 squamous cell lung carcino...

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