High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk
| Autor: | Wilbert H.M. Peters, Adriaan C.I.T.L. Tan, Hennie M.J. Roelofs, Polat Dura, Theo Wobbes, Ben J.M. Witteman, Rene H. M. te Morsche, Jody Salomon, Joost P.H. Drenth, Jon O. Kristinsson |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Esophageal Neoplasms Membrane transport and intracellular motility [NCMLS 5] Biology Adenocarcinoma Quality of Care [ONCOL 4] Risk Factors Internal medicine Genotype medicine Humans Genetic Predisposition to Disease Molecular gastro-enterology and hepatology Membrane transport and intracellular motility [IGMD 2] Allele Glucuronosyltransferase Molecular gastro-enterology and hepatology [IGMD 2] Carcinogen Genetic Association Studies Aged UGT2B4 Polymorphism Genetic Haplotype Case-control study Esophageal cancer Middle Aged medicine.disease Enzyme assay Endocrinology Oncology Haplotypes Case-Control Studies Immunology biology.protein Carcinoma Squamous Cell Female Molecular gastro-enterology and hepatology Translational research [IGMD 2] |
| Zdroj: | International Journal of Oncology, 40, 6, pp. 1789-96 International Journal of Oncology, 40, 1789-96 |
| ISSN: | 1019-6439 |
| Popis: | Contains fulltext : 108111.pdf (Publisher’s version ) (Open Access) Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Environmental and dietary factors have crucial roles in esophageal carcinogenesis. Polymorphisms in the UGT genes, a superfamily of enzymes essential for the detoxification of carcinogens, may alter enzyme activity and subsequently may play a role in EC etiology. Rather than solely establishing differences in genotype distribution, we investigated whether functional polymorphisms in UGT genes that can predict enzyme activity in vivo, may influence EC risk. A case-control study including 351 Caucasian EC patients and 592 Caucasian controls was conducted and polymorphisms in seven UGT genes were determined, using the polymerase chain reaction. On the basis of allelic in vitro enzyme activity measurements, genotypes were categorized according to their predicted in vivo enzyme activity into high, medium and low categories. Predicted enzyme activity groups were combined and compared between patients and controls. The UGT1A1 and UGT1A8 predicted high enzyme activity genotypes were significantly more (OR=1.62; 95% CI, 1.02-2.56) and less frequent (OR=0.36; 95% CI, 0.15-0.84) among patients with esophageal squamous cell carcinoma (ESCC), respectively. High (OR=0.42; 95% CI, 0.22-0.84) and medium (OR=0.25; 95% CI, 0.12-0.52) activity UGT2B4 genotypes were significantly less often present in ESCC patients. No association was detected between UGT genotypes and esophageal adenocarcinoma (EAC) risk. Polymorphisms in UGT genes, resulting in altered enzyme activity genotypes, do not seem modifiers of EAC risk. However, the predicted high activity UGT1A1 genotype, associated with low serum levels of the antioxidant bilirubin, was associated with an increased ESCC risk. The UGT1A8 and UGT2B4 genotypes associated with decreased predicted enzyme activities, were significantly associated with an increased risk of ESCC, probably by a decreased detoxification of carcinogens. 01 juni 2012 |
| Databáze: | OpenAIRE |
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