The Effect ofCYP, GST,andSULTPolymorphisms and Their Interaction with Smoking on the Risk of Hepatocellular Carcinoma

Abstract

Aim. The aim of our study was to assess whether selected single nucleotide polymorphisms ofCYP1A1and2E1,GSTM1,GSTT1, andSULT1A1influence susceptibility towards HCC, considering their interaction with cigarette smoking.Methods. We recruited HCC cases and controls among patients admitted to the hospital “Agostino Gemelli,” from January 2005 until July 2010. Odds ratios (OR) of HCC were derived from unconditional multiple logistic regression. Gene-gene and gene-smoking interaction were quantified by computing the attributable proportion (AP) due to biological interaction.Results. The presence of anyCYP2E1*5Bvariant allele (OR: 0.23; 95% CI: 0.06-0.71) andCYP2E1*6variant allele (OR: 0.08; 95% CI: 0.01–0.33) was inversely related to HCC. There was a borderline increased risk among carriers of combinedCYP1A1*2AandSULT1A1variant alleles (OR: 1.67; 95% CI: 0.97–3.24). A significant biological interaction was observed betweenGSTT1and smoking (AP = 0.48; 95% CI: 0.001–0.815), with an OR of 3.13 (95% CI: 1.69–5.82), and borderline significant interaction was observed forSULT1A1and smoking (AP = 0.36; 95% CI: −0.021–0.747), with an OR of 3.05 (95% CI: 1.73–5.40).Conclusion.CYP2E1*5BandCYP2E1*6polymorphisms have a favourable effect on the development of HCC, while polymorphisms ofGSTT1andSULT1A1might play role in increasing the susceptibility among smokers.