SAGE-Hindawi Access to Research Journal of Nucleic Acids Volume 2010, Article ID 386798, 7 pages doi:10.4061/2010/386798 Research Article Smoking, DNA Adducts and Number of Risk DNA Repair Alleles in Lung Cancer Cases, in Subjects with Benign Lung Diseases and in Controls Marco Peluso,1 Armelle Munnia,1 Sara Piro,1 Alessandra Armillis,1 Marcello Ceppi,2 Giuseppe Matullo,3, 4 and Riccardo Puntoni2 1 Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, ISPO—Cancer Prevention and Research Institute, Via Cosimo il Vecchio N.2, 50139 Florence, Italy 2 Molecular Epidemiology Unit, National Cancer Research Institute, 16132 Genoa, Italy 3 Department of Genetics, Biology and Biochemistry, Faculty of Medicine and Surgery, University of Turin, 10124 Turin, Italy 4 Section of Epidemiology, ISI Foundation—Institute for Scientiﬁc Interchange, Villa Gualino, 10133 Turin, Italy Correspondence should be addressed to Marco Peluso, m.peluso@ispo.toscana.it Received 14 May 2010; Revised 8 July 2010; Accepted 28 July 2010 Academic Editor: Shigenori Iwai Copyright © 2010 Marco Peluso et al. This 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. Smoke constituents can induce DNA adducts that cause mutations and lead to lung cancer. We have analyzed DNA adducts and polymorphisms in two DNA repair genes, for example, XRCC1 Arg194Trp and Arg399Gln genes and XRCC3 Thr241Met gene, in 34 lung cancer cases in respect to 30 subjects with benign lung cancer disease and 40 healthy controls. When the study population was categorized in base to the number of risk alleles, adducts were signiﬁcantly increased in individuals bearing 3-4 risk alleles (OR = 4.1 95% C.I. 1.28–13.09, P = .009). A signiﬁcant association with smoking was noticed in smokers for more than 40 years carrying 3-4 risk alleles (OR = 36.38, 95% C.I. 1.17–1132.84, P = .040). A not statistically signiﬁcant increment of lung cancer risk was observed in the same group (OR = 4.54, 95% C.I. 0.33–62.93, P = .259). Our results suggest that the analysis of the number of risk alleles predicts the interindividual variation in DNA adducts of smokers and lung cancer cases. 1. Introduction Lung cancer is a leading cause of cancer death in the world [1]. Advances in the treatment of locally advanced lung cancer had no impact on overall 5-year survival rates from this disease that remains only of 15%. Although the rates of lung cancer mortality have started to decrease in countries where smoking habits have been modiﬁed, the projections are not optimistic because of the recent surge in tobacco consumption among young people. In addition, even if smoking habits could be modiﬁed signiﬁcantly, the long lag time between peak of tobacco consumption and the development of lung cancer will assure a long life for this epidemic. The role of tobacco smoking in the aetiology of lung cancer has been widely evaluated [2]. Many compounds present in the smoke of cigarettes, such as the polycyclic aromatic hydrocarbons (PAH), induce DNA adducts after metabolic activation [3]. Unrepaired DNA adducts can cause mutations, including mutational hot spots in p53 tumour suppressor gene [4], and lead to unregulated cell growth and cancer. Increased DNA adduct levels have been suggested to be predictive of lung cancer risk, reﬂecting both the environmental exposure to carcinogens than individual susceptibility [5–8]. It has been hypothesized that interindividual diﬀerence in lung cancer risk may be due to diﬀerences in DNA repair. In support of this hypothesis, diﬀerent studies have indicated that DNA variation in DNA repair genes may inﬂuence cancer susceptibility [9]. Our group has conducted a number of studies that have shown associations between DNA polymorphisms in DNA repair genes, mainly in XRCC1 (X- ray repair cross complementing) and XRCC3 genes, cancer, and/or DNA adducts [10–14] and unpublished results.