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

Abstract

1. 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).

2. 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.

3. 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.

4. Age over 48 years, alcohol consumption, and the presence of polymorphic variants of GSTP1 and GSTT1 were associated with the risk of developing HCC.

Keywords:

• Single-nucleotide polymorphism
• xenobiotic metabolism
• hepatocellular carcinoma
• epoxide hydrolase
• glutathione S-transferase

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that supported the findings of this study are available from the corresponding author EMG-B upon request.

Additional information

Funding

This work was supported by the National Council of Technological and Scientific Development (CNPq) under Grant number 310582/2014-8 and 310987/2018-0; the São Paulo Research Foundation (FAPESP) under Grant numbers 2012/14781-1 and 2012/02473-0; and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The study was also supported by FAMERP/FUNFARME.