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Evaluation of polymorphisms of xenobiotic metabolizing genes (GSTM1, GSTT1, GSTP1 e mEH) in patients with cirrhosis and hepatocellular carcinoma

Abstract

The most frequent primary tumor of the liver is hepatocellular carcinoma, also called hepatocellular carcinoma (HCC). The molecular events that initiate the hepatocellular carcinogenesis correlate with diseases that interfere with DNA synthesis, such as cirrhosis, and infection by VHB and VHS (hepatitis viruses B and C). Some individuals may be at increased risk of developing cancer due to differences in biometabolism. Thus, individual differences may present itself as a significant risk factor for cancers related to smoking. Recent approaches have associated gene polymorphisms of metabolizing xenobiotics such as members of the family of glutathione S-transferases (GSTs), and the family of microsomal epoxide hydrolase (1 mEHs) with hepatocellular carcinoma. However, further studies are needed to elucidate this association. This study aims to identify the genotypes of restriction genes GSTM1, GSTT1 and GSTP1, mEH and the C341T polymorphism in patients with hepatocellular carcinoma and in individuals with no history of cancer (control group), to identify biomarkers of susceptibility to this cancer. In this proposal, will be evaluated 150 patients with pathologic diagnosis for cirrhosis or hepatocellular carcinoma and blood samples from 500 control subjects. The variables to be analyzed are: Virus B, C virus, alcohol consumption, steatohepatitis, autoimmune hepatitis, hemochromatosis and Wilson's disease. Genotyping of polymorphisms will be performed by Polymerase Chain Reaction - Length Polymorphisms Restriction Fragment (PCR-RFLP). The molecular findings and information about risk factors will be evaluated statistically. The results may help to clarify the role of genetic differences in susceptibility to the effects of carcinogens and identify biomarkers of susceptibility. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERREIRA, GISLAINE DIONISIO; DE MENDONCA FERNANDES, GLAUCIA MARIA; PENTEADO, CAMILA; CORIA, VIVIAN ROMANHOLI; DA SILVA GALBIATTI-DIAS, ANA LIVIA; RUSSO, ANELISE; URBANIN CASTANHOLE-NUNES, MARCIA MARIA; DA SILVA, RENATO FERREIRA; MARTINS ALVES DA SILVA, RITA DE CASSIA; PAVARINO, ERIKA CRISTINA; RUIZ CINTRA, MARIANGELA TORREGLOSA; GOLONI-BERTOLLO, ENY MARIA. Polymorphisms in xenobiotic metabolism-related genes in patients with hepatocellular carcinoma: a case-control study. XENOBIOTICA, v. 51, n. 6, p. 737-744, JUN 3 2021. Web of Science Citations: 0.
ZARA-LOPES, TAIRINE; SILVA GALBIATTI-DIAS, ANA LIVIA; URBANIN CASTANHOLE-NUNES, MARCIA M.; PADOVANI-JUNIOR, JOAO ARMANDO; MANIGLIA, JOSE VICTOR; PAVARINO, ERIKA CRISTINA; GOLONI-BERTOLLO, ENY MARIA. Polymorphisms in MTHFR, MTR, RFC1 and C beta S genes involved in folate metabolism and thyroid cancer: a case-control study. Archives of Medical Science, v. 15, n. 2, p. 522-530, MAR 2019. Web of Science Citations: 0.
ZARA-LOPES, T.; GIMENEZ-MARTINS, A. P. A.; NASCIMENTO-FILHO, C. H. V.; CASTANHOLE-NUNES, M. M. U.; GALBIATTI-DIAS, A. L. S.; PADOVANI-JUNIOR, J. A.; MANIGLIA, J. V.; FRANCISCO, J. L. E.; PAVARINO, E. C.; GOLONI-BERTOLLO, E. M. Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development. Genetics and Molecular Research, v. 15, n. 2 2016. Web of Science Citations: 8.

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