BACKGROUND: Differences in genotype and phenotype of detoxification genes could be one reason for conflicting results in studies dealing with gene polymorphisms as susceptibility factors for tobacco associated cancer. OBJECTIVES: The objective of this study was to investigate gene polymorphisms of detoxification enzymes and to determine whether the enzyme concentration and activity of glutathione S transferase microliter 1 correlates with the genotype in patients with cancer of the oral cavity. MATERIAL AND METHODS: In 73 cancer patients and 136 matched healthy controls, the polymorphisms of glutathione S-transferase mu1 and theta (GSTM/GSTT), cytochrome p450 1A1 and CYP2D6 were detected. Simultaneously, GSTM1 protein concentration and total GSTM1-activity were determined. RESULTS: Only the coincidence of GSTM1 and GSTT null genotype was associated with oral cavity cancer. GSTM1 protein concentration and enzyme activity in null-genotype patients was significantly lower than in GSTM1-allele-carrier. But the enzyme concentration did not correlate with the activity. CONCLUSION: We assume that detoxification enzymes are functionally redundant and that only the simultaneous deficiency of several detoxification enzymes increases the risk for oral cancer.
BACKGROUND: Differences in genotype and phenotype of detoxification genes could be one reason for conflicting results in studies dealing with gene polymorphisms as susceptibility factors for tobacco associated cancer. OBJECTIVES: The objective of this study was to investigate gene polymorphisms of detoxification enzymes and to determine whether the enzyme concentration and activity of glutathione S transferase microliter 1 correlates with the genotype in patients with cancer of the oral cavity. MATERIAL AND METHODS: In 73 cancerpatients and 136 matched healthy controls, the polymorphisms of glutathione S-transferase mu1 and theta (GSTM/GSTT), cytochrome p450 1A1 and CYP2D6 were detected. Simultaneously, GSTM1 protein concentration and total GSTM1-activity were determined. RESULTS: Only the coincidence of GSTM1 and GSTT null genotype was associated with oral cavity cancer. GSTM1 protein concentration and enzyme activity in null-genotype patients was significantly lower than in GSTM1-allele-carrier. But the enzyme concentration did not correlate with the activity. CONCLUSION: We assume that detoxification enzymes are functionally redundant and that only the simultaneous deficiency of several detoxification enzymes increases the risk for oral cancer.
Authors: Elisa Pastore; Federica Perrone; Marta Orsenigo; Luigi Mariani; Clara Millefanti; Stefano Riccio; Sarah Colombo; Giulio Cantù; Marco A Pierotti; Silvana Pilotti Journal: Transl Oncol Date: 2009-05 Impact factor: 4.243
Authors: Leonor Varela-Lema; Emanuela Taioli; Alberto Ruano-Ravina; Juan M Barros-Dios; Devasena Anantharaman; Simone Benhamou; Stefania Boccia; Rajani A Bhisey; Gabriella Cadoni; Ettore Capoluongo; Chien-Jen Chen; William Foulkes; Eny Maria Goloni-Bertollo; Ana Hatagima; Richard B Hayes; Takahiko Katoh; Sergio Koifman; Phillip Lazarus; Johannes J Manni; Manoj Mahimkar; Shunji Morita; Jong Park; Kwang-Kyun Park; Erika Cristina Pavarino Bertelli; Enilze Maria de Souza Fonseca Ribeiro; Bidyut Roy; Margaret R Spitz; Richard C Strange; Qingyi Wei; Camille C Ragin Journal: Genet Med Date: 2008-06 Impact factor: 8.822