Research Article The Effect of CYP, GST, and SULT Polymorphisms and Their Interaction with Smoking on the Risk of Hepatocellular Carcinoma Stefania Boccia, 1,2 Luca Miele, 3,4 Nikola Panic, 1,5 Federica Turati, 6 Dario Arzani, 1 Consuelo Cefalo, 3 Rosarita Amore, 1 Milutin Bulajic, 5,7 Maurizio Pompili, 8 Gianlodovico Rapaccini, 3,4 Antonio Gasbarrini, 8 Carlo La Vecchia, 9 and Antonio Grieco 3 1 Institute of Public Health, Section of Hygiene, Department of Public Health, Universit` a Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy 2 IRCCS San Rafaele Pisana, Via della Pisana 235, 00163 Rome, Italy 3 Institute of Internal Medicine, Gemelli Hospital, Universit` a Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy 4 Internal Medicine and Gastroenterology Unit, Complesso Integrato Columbus, Via Giuseppe Moscati 31-33, 00168 Rome, Italy 5 University Clinical-Hospital Center “Dr Dragisa Misovic-Dedinje”, Milana Tepica 1, 11000 Belgrade, Serbia 6 Department of Epidemiology, IRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156 Milan, Italy 7 Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia 8 Internal Medicine and Gastroenterology Division, Gemelli Hospital, Universit` a Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy 9 Department of Clinical Sciences and Community Health, Universit` a degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy Correspondence should be addressed to Stefania Boccia; sboccia@rm.unicatt.it Received 16 April 2014; Revised 19 June 2014; Accepted 19 June 2014 Academic Editor: Paolo Bofetta Copyright © Stefania Boccia et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. he aim of our study was to assess whether selected single nucleotide polymorphisms of CYP1A1 and 2E1, GSTM1, GSTT1, and SULT1A1 inluence 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 quantiied by computing the attributable proportion (AP) due to biological interaction. Results. he presence of any CYP2E1 ∗ 5B variant allele (OR: 0.23; 95% CI: 0.06-0.71) and CYP2E1 ∗ 6 variant allele (OR: 0.08; 95% CI: 0.01–0.33) was inversely related to HCC. here was a borderline increased risk among carriers of combined CYP1A1 ∗ 2A and SULT1A1 variant alleles (OR: 1.67; 95% CI: 0.97–3.24). A signiicant biological interaction was observed between GSTT1 and smoking (AP = 0.48; 95% CI: 0.001–0.815), with an OR of 3.13 (95% CI: 1.69–5.82), and borderline signiicant interaction was observed for SULT1A1 and smoking (AP = 0.36; 95% CI: −0.021– 0.747), with an OR of 3.05 (95% CI: 1.73–5.40). Conclusion. CYP2E1 ∗ 5B and CYP2E1 ∗ 6 polymorphisms have a favourable efect on the development of HCC, while polymorphisms of GSTT1 and SULT1A1 might play role in increasing the susceptibility among smokers. 1. Introduction Hepatocellular carcinoma (HCC) is currently the sixth most common cancer and the third cause of cancer deaths world- wide [1]. Its prognosis remains poor, with a 5-year survival rate less than 20% in Europe [2]. Risk factors for HCC include infection with hepatitis B (HBV) and hepatitis C viruses (HCV), history of diabetes mellitus, nonalcoholic fatty liver disease and cirrhosis, heavy alcohol consumption, and cigarette smoking [3–5]. Cofee consumption appears to have a favorable efect [6]. Further, genetic factors appear to modulate the individual susceptibility as the siblings of HCC Hindawi Publishing Corporation BioMed Research International Article ID 179867