Peluso Marco, Munnia Armelle, Piro Sara, Armillis Alessandra, Ceppi Marcello, Matullo Giuseppe, Puntoni Riccardo
Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, ISPO-Cancer Prevention and Research Institute, Via Cosimo il Vecchio N.2, 50139 Florence, Italy.
J Nucleic Acids. 2010 Oct 4;2010:386798. doi: 10.4061/2010/386798.
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.
烟雾成分可诱导DNA加合物的形成,这些加合物会导致突变并引发肺癌。我们分析了34例肺癌患者、30例良性肺部疾病患者以及40名健康对照者中两个DNA修复基因的DNA加合物及多态性,这两个基因分别是XRCC1基因的Arg194Trp和Arg399Gln位点以及XRCC3基因的Thr241Met位点。当根据风险等位基因数量对研究人群进行分类时,携带3 - 4个风险等位基因的个体中,DNA加合物显著增加(比值比=4.1,95%置信区间1.28 - 13.09,P = 0.009)。对于吸烟超过40年且携带3 - 4个风险等位基因的吸烟者,发现其与吸烟存在显著关联(比值比=36.38,95%置信区间1.17 - 1132.84,P = 0.040)。在同一组中观察到肺癌风险有非统计学显著的增加(比值比=4.54,95%置信区间0.33 - 62.93,P = 0.259)。我们的结果表明,对风险等位基因数量的分析可预测吸烟者和肺癌患者DNA加合物的个体间差异。