Polymorphisms in xenobiotic metabolism-related genes in patients with hepatocellular carcinoma: a case-control study

• Published in: Xenobiotica Vol. 51; no. 6; pp. 737 - 744
• Main Authors: Ferreira, Gislaine Dionísio, Fernandes, Glaucia Maria de Mendonça, Penteado, Camila, Cória, Vivian Romanholi, Galbiatti-Dias, Ana Lívia da Silva, Russo, Anelise, Castanhole-Nunes, Márcia Maria Urbanin, Silva, Renato Ferreira da, Silva, Rita de Cássia Martins Alves da, Pavarino, Érika Cristina, Torreglosa Ruiz Cintra, Mariangela, Goloni-Bertollo, Eny Maria
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-06-2021
• Subjects: Carcinoma, Hepatocellular - genetics; Case-Control Studies; epoxide hydrolase; Genetic Predisposition to Disease; Genotype; glutathione S-transferase; Glutathione Transferase - genetics; hepatocellular carcinoma; Humans; Liver Neoplasms - genetics; Middle Aged; Risk Factors; Single-nucleotide polymorphism; xenobiotic metabolism; Xenobiotics; Single-nucleotide polymorphism; epoxide hydrolase; glutathione S-transferase; hepatocellular carcinoma; xenobiotic metabolism
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498254.2021.1893408

This study was performed to investigate the relationship between polymorphisms in microsomal epoxide hydrolase (mEH; Tyr113His and His139Arg substitution) and glutathione S-transferase (GST; GSTM1 deletion, GSTT1 deletion, and GSTP1.Ala114Val substitution) and their correlation with clinico-histopathological features in hepatocellular carcinoma (HCC).
We evaluated environmental risk factors and genetic alterations in 556 individuals (86 cases and 470 controls). PCR multiplex for GSTM1 and GSTT1, polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for GSTP1, and real-time PCR for mEH were performed. Statistical analyses were performed using multiple logistic regression tests.
Age over 48 years (p < 0.001) and alcohol consumption (p = 0.021) were the predictors of increased risk of developing HCC. GSTP1.Ala114Val for all regression models (p < 0.05), except the recessive model, and the GSTT1 null genotype (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.21-0.87, p = 0.019) were predictors of an increased risk of developing HCC. Polymorphic GSTT1, GSTM1, GSTP1.Ala114Val, and mEH.His139Arg and wild-type mEH.Tyr113His (OR = 5.04; 95% CI = 1.59-16.04; p = 0.006) were associated with HCC.
Age over 48 years, alcohol consumption, and the presence of polymorphic variants of GSTP1 and GSTT1 were associated with the risk of developing HCC.