碱基切除修复和核苷酸切除修复基因多态性与肺癌风险的关系。
Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk.
作者信息
De Ruyck Kim, Szaumkessel Marcin, De Rudder Isabelle, Dehoorne Annelore, Vral Anne, Claes Kathleen, Velghe Anja, Van Meerbeeck Jan, Thierens Hubert
机构信息
Department of Anatomy, Embryology, Histology and Medical Physics, Ghent University, Proeftuinstraat 86, B-9000 Gent, Belgium.
出版信息
Mutat Res. 2007 Jul 28;631(2):101-10. doi: 10.1016/j.mrgentox.2007.03.010. Epub 2007 Apr 21.
Polymorphisms in DNA repair genes may be associated with differences in DNA repair capacity, thereby influencing the individual susceptibility to smoking-related cancer. We investigated the association of 10 base-excision and nucleotide-excision repair gene polymorphisms (XRCC1 -77 T/C, Arg194Trp, Arg280His and Arg399Gln; APE1 Asp148Glu; OGG1 Ser326Cys; XPA -4 G/A; XPC PAT; XPD Asp312Asn and Lys751Gln) with lung cancer risk in Caucasians. Genotypes were determined by PCR-RFLP and PCR-single base extension assays in 110 lung cancer patients and 110 age- and sex-matched controls, and the results were analyzed using logistic regression adjusted for relevant covariates. A significant association between the APE1 Asp148Glu polymorphism and lung cancer risk was found, with adjusted odds ratios (OR) of 3.38 (p=0.001) for the Asp/Glu genotype and 2.39 (p=0.038) for the Glu/Glu genotype. Gene-smoking interaction analyses revealed a statistically significant interaction between cumulative cigarette smoking and the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms: these polymorphisms were significantly associated with lung cancer in nonsmokers and light smokers (<25 PY; OR=4.92, p=0.021 for XRCC1 399 Gln/Gln; OR=3.62, p=0.049 for XPD 751 Gln/Gln), but not in heavy smokers (> or =25 PY; OR=0.68, p=0.566 for XRCC1 399 Gln/Gln; OR=0.46, p=0.295 for XPD 751 Gln/Gln). Both the XRCC1 Arg194Trp and Arg280His as well as the OGG1 Ser326Cys heterozygous genotypes were associated with a significantly reduced risk for lung cancer (OR=0.32, p=0.024; OR=0.25, p=0.028; OR=0.51, p=0.033, respectively). No associations with lung cancer risk were found for the XRCC1 -77 T/C, the XPA -4 G/A and the XPC PAT polymorphisms. In conclusion, the APE1 Asp148Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCC1 Arg399Gln and the XPD Lys751Gln polymorphisms and lung cancer risk.
DNA修复基因中的多态性可能与DNA修复能力的差异相关，从而影响个体对吸烟相关癌症的易感性。我们研究了10种碱基切除和核苷酸切除修复基因多态性（XRCC1 -77 T/C、Arg194Trp、Arg280His和Arg399Gln；APE1 Asp148Glu；OGG1 Ser326Cys；XPA -4 G/A；XPC PAT；XPD Asp312Asn和Lys751Gln）与白种人肺癌风险的关联。通过PCR-RFLP和PCR单碱基延伸分析确定了110例肺癌患者和110例年龄及性别匹配对照的基因型，并使用针对相关协变量进行调整的逻辑回归分析结果。发现APE1 Asp148Glu多态性与肺癌风险之间存在显著关联，Asp/Glu基因型的调整优势比（OR）为3.38（p = 0.001），Glu/Glu基因型的调整优势比为2.39（p = 0.038）。基因-吸烟相互作用分析显示，累积吸烟与XRCC1 Arg399Gln和XPD Lys751Gln多态性之间存在统计学显著的相互作用：这些多态性在不吸烟者和轻度吸烟者（<25包年；XRCC1 399 Gln/Gln的OR = 4.92，p = 0.021；XPD 751 Gln/Gln的OR = 3.62，p = 0.049）中与肺癌显著相关，但在重度吸烟者（≥25包年；XRCC1 399 Gln/Gln的OR = 0.68，p = 0.566；XPD 751 Gln/Gln的OR = 0.46，p = 0.295）中则不然。XRCC1 Arg194Trp和Arg280His以及OGG1 Ser326Cys杂合基因型均与肺癌风险显著降低相关（分别为OR = 0.32，p = 0.024；OR = 0.25，p = 0.028；OR = 0.51，p = 0.033）。未发现XRCC1 -77 T/C、XPA -4 G/A和XPC PAT多态性与肺癌风险存在关联。总之，APE1 Asp148Glu多态性对肺癌具有高度预测性，累积吸烟改变了XRCC1 Arg399Gln和XPD Lys751Gln多态性与肺癌风险之间的关联。
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