Avaliação de polimorfismos dos genes CYP1A1 e CYP2E1 no risco para cirrose hepática e carcinoma hepatocelular

Abstract

Liver cancer ranks fifth in incidence and third in mortality worldwide. Most new cases and deaths occur in developing countries. Cirrhosis is a major risk factor for hepatocellular carcinoma (HCC). Several studies have shown that polymorphisms in cytochrome P450 (CYPs) genes can contribute to the etiology of complex diseases, as well as liver cancer. Polymorphisms in the genes of this family can alter the expression or function of the protein and influence the individual levels of detoxification, which contribute to the development of liver diseases. Objective: To investigate the association between the genetic polymorphisms CYP1A1*2A (rs4646903), CYP1A1*2C (rs1048943), CYP2E1*5B (rs2031920), CYP1E1*6 (rs6413432) and the risk of hepatic cirrhosis and HCC. Casuistic and Methods: Seven hundred and forty-five subjects (160 cirrhosis patients, 97 HCC patients and 488 controls) were evaluated. Polymorphisms were investigated by polymerase chain reaction / restriction fragment length polymorphism (PCR-RFLP) and Real-Time PCR. Statistical analyses were performed by chi-square and binary logistic regression. Survival analysis was performed using Kaplan Meier curve and Log rank test. Results: The results showed that age ≥ 60 years was associated with HCC (OR = 12.22, 95% CI: 7.17-20.82, p <0.001) and age ≥57 years was a risk factor for cirrhosis (OR = 7.12 CI 95% 4.68-10.84, p <0.001). Hepatitis B (OR = 7.84, 95% CI: 1.86-33.08, p = 0.005) and alpha fetoprotein> 500 ng / mL (OR = 3.73, 95% CI: 1.25-11, 13; p = 0.018) were associated with HCC. The polymorphisms CYP1A1 *2A, CYP1A1 *2C, CYP2E1 *5B and CYP2E1 *6 were not associated with risk of HCC and cirrhosis (p> 0.05), as well as CYP1A1 and CYP2E1 haplotypes (p > 0.05). There was no interaction between polymorphisms and smoking or alcohol consumption in the risk for HCC and cirrhosis (p> 0.05). No association was found between the polymorphisms and clinical parameters in HCC patients (p> 0.05). CYP2E1 *5B and CYP2E1 *6 polymorphisms were associated with a reduction in survival in HCC patients (p = 0.0234 and p = 0.0424, respectively). Conclusion: This study concludes that age is associated with the risk of developing HCC and cirrhosis, and CYP2E1 *5B and CYP2E1 *6 polymorphisms contribute for the reduced survival in HCC patients.