Journal of Nucleic Acids Gender Womanc Male Age (years) Per unit Smoking habit Nonsmokerc Former smoker Smoker <40 years Smoker ≥40 years Status Controlsc Benign lung disease Lung cancer XRCC1 Arg194Trp XRCC1 Arg399Gln XRCC3 Thr241Met Number of risk alleles Arg/Argc Arg/Trp Arg/Argc Arg/Gln Gln/Gln Thr/Thrc Thr/Met Met/Met 0-1c 2 3-4 N a 31 73 104 21 44 11 27 40 30 34 87 11 37 47 12 40 41 19 25 31 38 1.2 ± 0.3 1.3 ± 0.2 1.3 ± 0.2 0.8 ± 0.4 1.0 ± 0.3 1.5 ± 0.7 2.0 ± 0.5 1.0 ± 0.3 1.3 ± 0.4 1.5 ± 0.4 1.1 ± 0.2 2.6 ± 1.1 0.9 ± 0.2 1.4 ± 0.3 1.8 ± 1.0 1.5 ± 0.4 1.2 ± 0.3 0.7 ± 0.4 0.8 ± 0.4 1.0 ± 0.3 2.0 ± 0.5 1 0.65 1.02 1 1.60 2.38 5.28 1 0.93 1.17 1 4.08 1 0.93 1.32 1 0.38 0.17 1 0.92 4.1 Table 1: Means of DNA adducts ± standard error (SE) for diﬀerent variables considered in the study plus the parameter estimates of the multivariate regression model. Meansb ± S.E. Odds Ratio aSome ﬁgures do not add up to the total because of missing values. bLevels per 108 normal nucleotides. cReference level. The choice was based on the diﬀerent association of XRCC1 and XRCC3 polymorphisms with lung cancer risk, for example, positive for XRCC1 Arg194Trp and Arg399Gln and negative for XRCC3 Met241Met [9, 16, 17]. The analysis of the eﬀect of diﬀerent combinations of DNA repair single nucleotide polymorphisms on DNA adducts has been performed under the assumption that the combination of diﬀerent polymorphisms can have additive or more than additive eﬀects. When the study population was categorized in base to the number of risk alleles, the levels of DNA adducts were statistically signiﬁcantly increased in individuals bearing three-four 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). A signiﬁcant trend with increasing the number of risk alleles was also observed (P for trend <.05). Any association with benign lung diseases was not found. Tobacco smoking is recognised as the primary pre- ventable cause of human cancer. Therefore, many studies have explored the inﬂuence of smoking on the levels of DNA adducts in nucleated blood cells in order to identify an early and sensitive biomarker of eﬀective intake of tobacco carcinogens [18]. In our study, we have analyzed PBLs as surrogate and more accessible tissues than bronchial biopsies, and we compared the levels of DNA adducts in patients with lung cancer in respect to those with benign lung diseases and controls. Our aim was to evaluate whether the levels of C.I. 0.19–2.16 0.97–1.06 0.39–6.58 0.41–13.90 1.00–27.72 0.28–3.03 0.39–3.47 0.77–21.48 0.36–2.39 0.34–5.18 0.15–0.97 0.05–0.61 0.31–2.69 1.28–13.09 3 P-value .480 .516 .517 .336 .049 .898 .783 .098 .882 .689 .043 .006 .877 .009