Carcinogenesis Advance Access originally published online on July 28, 2005
Carcinogenesis 2005 26(12):2157-2163; doi:10.1093/carcin/bgi195
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Carcinogenesis vol.26 no.12 © Oxford University Press 2005; all rights reserved.
Glutathione S-transferase T1 polymorphisms are associated with outcome in colorectal cancer
Human Genomics Research Group, Institute of Science and Technology in Medicine, University of Keele, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire, ST4 7PA, UK
* To whom correspondence should be addressed. Tel: +44 0 1782 554669; Fax: +44 0 1782 554646; Email: Anthony.Fryer{at}uhns.nhs.uk
Colorectal cancer (CRC) remains a significant cause of mortality accounting for 
10% of all deaths from malignancy in the western world. Polymorphism in the glutathione S-transferase GSTT1 gene has been associated with CRC risk in some but not all studies. In this study, we examined associations between GSTT1 genotypes and CRC risk, and prognosis in 361 cases and 881 unrelated controls. GSTT1 null was associated with a small but significant increase in risk (P = 0.0006, odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.22–2.24). GSTT1 null was also associated with a significantly younger age at diagnosis (mean 65.2 years) compared with GSTT1 A (mean 67.6 years, P = 0.031). There were no significant associations between GSTT1 genotypes and clinical factors (e.g. Dukes stage, differentiation and tumour node metastasis classification) in the total case group. However, following stratification by age (<70 versus 
70 years at diagnosis), in the patients diagnosed <70 years of age, GSTT1 null was more common in Dukes grade A/B tumours (P = 0.046), stage T1/T2 tumours (P = 0.053) and those with a pushing margin (P = 0.066). We also identified associations between GSTT1 null and increased prevalence of host lymphocyte response, particularly in the younger patients (P = 0.036). Furthermore, GSTT1 null was associated with improved survival in younger patients (P = 0.017, hazards ratio (HR) = 0.52, 95% CI = 0.31–0.89) but poorer survival in older patients (P = 0.017, HR = 1.89, 95% CI = 1.12–3.20). We proposed a model based on the dual functionality of GSTT1 to explain these contrasting results. We suggest that the null genotype is associated with improved immune response in younger patients, but poorer detoxification in older patients. These findings may also provide an explanation for the contrasting finding of other studies on the role of this gene in CRC.
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