Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Mala Hora 4, 036 01, Martin, Slovak Republic.
Mol Biol Rep. 2013 Sep;40(9):5261-73. doi: 10.1007/s11033-013-2626-z. Epub 2013 May 15.
Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01).
核苷酸和碱基切除修复基因的多态性与肺癌发病风险的变异性有关。本研究旨在探讨以下选定的 DNA 修复基因的多态性：XPC（Lys939Gln）、XPD（Lys751Gln）、hOGG1（Ser326Cys）和 XRCC1（Arg399Gln），并强调在斯洛伐克人群中性别差异对它们的影响。我们分析了 761 名个体，包括 382 名确诊为肺癌的患者和 379 名健康对照者。通过聚合酶链反应/限制性片段长度多态性方法确定基因型。我们发现，男女之间的肺癌发病风险存在统计学上的显著差异。女性携带 XPC Gln/Gln、XPC Lys/Gln+Gln/Gln 和 XRCC1 Arg/Gln、XRCC1 Arg/Gln+Gln/Gln 基因型，患肺癌的风险显著增加，对应的 OR 值分别为 2.06（p=0.04）、1.66（p=0.04）和 1.62（p=0.04）、1.69（p=0.02）。总的来说，我们发现以下基因型组合的肺癌发病风险显著增加：XPD Lys/Gln+XPC Lys/Lys（OR=1.62；p=0.04）和 XRCC1 Gln/Gln+hOGG1 Ser/Ser（OR=2.14；p=0.02）。在按性别分层后，我们发现以下基因型组合在男性中具有统计学意义：XPD Lys/Gln+XPC Lys/Lys（OR=1.87；p=0.03）、XRCC1 Arg/Gln+XPC Lys/Lys（OR=4.52；p=0.0007）和 XRCC1 Arg/Gln+XPC Lys/Gln（OR=5.44；p<0.0001）。在女性中，我们发现以下不同基因型组合具有统计学意义：XRCC1 Arg/Gln+hOGG1 Ser/Ser（OR=1.98；p=0.04）、XRCC1 Gln/Gln+hOGG1 Ser/Ser（OR=3.75；p=0.02）、XRCC1 Arg/Gln+XPC Lys/Gln（OR=2.40；p=0.04）和 XRCC1 Arg/Gln+XPC Gln/Gln（OR=3.03；p=0.04）。我们发现，女性患者和健康对照组之间的基因型组合降低了癌症风险：XPD Lys/Lys+XPC Lys/Gln（OR=0.45；p=0.02）、XPD Lys/Gln+XPC Lys/Lys（OR=0.32；p=0.005）和 XPD Lys/Gln+XPC Lys/Gln（OR=0.48；p=0.02）。我们的结果显示，在观察到的与肺癌风险相关的基因多态性中，吸烟和不吸烟的患者之间没有差异。然而，性别分层表明，hOGG1 基因（Ser/Cys）杂合状态可能对女性非吸烟者的肺癌风险有影响（OR=0.20；p=0.01），XPC 基因（Lys/Gln）杂合状态可能对男性吸烟者的肺癌风险有影响（OR=2.70；p=0.01）。
