Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk
Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk
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DOI：
10.1016/j.mrgentox.2007.03.010
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发表时间：
2007-07-28
影响因子：
1.9
通讯作者：
Thierens, Hubert
中科院分区：
文献类型：
--
作者：
De Ruyck, Kim;Szaumkessel, Marcin;Thierens, Hubert
DNA修复基因的多态性可能与DNA修复能力的差异有关，从而影响个体对吸烟相关癌症的易感性。我们研究了10个碱基切除和核苷酸切除修复基因多态性（XRCCI-77 T/C，Arg 194 Trp，Arg 28 OHis和Arg 399 Gln; APEI Asp 148 Glu; OGG 1 Ser 326 Cys; XPA-4 G/A; XPC PAT：XPD Asp 312 Asn和Lys 75 I Gln）与高加索人肺癌风险的关系。通过PCR-RFLP和PCR-单碱基延伸分析确定110例肺癌患者和110例年龄和性别匹配的对照的基因型，并使用Logistic回归分析调整相关协变量的结果。APE 1 Asp 148 Glu多态性与肺癌风险显著相关，Asp/Glu基因型和Glu/Glu基因型的校正比值比（OR）分别为3.38（P = 0.001）和2.39（P = 0.038）。基因-吸烟相互作用分析揭示了累积吸烟与XRCC 1 Arg 399 Gln和XPD Lys 75 I Gln多态性之间的统计学显著相互作用：这些多态性与非吸烟者和轻度吸烟者的肺癌显著相关。（< 25 PY，XRCC 1 399 Gln/Gln OR = 4.92，p = 0.021; XPD 751 Gln/Gln OR = 3.62，p = 0.049），但在重度吸烟者中未发现（>= 25 PY;对于XRCC 1 399 GWGln，OR = 0.68，p = 0.566;对于XPD 751 Gln/Gln，OR = 0.46，p = 0.295）。XRCC 1 Arg 194 Trp和Arg 28 OHis以及OGG 1 Ser 326 Cys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XRCC 1 -77 T/C、XPA-4 G/A和XPC PAT多态性与肺癌风险相关。总之，APEI Aspl 48 Glu多态性对肺癌具有高度预测性，并且累积吸烟改变了XRCCl Arg 399 Gln和XPD Lys 75 I Gln多态性与肺癌风险之间的关联。(c)2007 Elsevier B. V.保留所有权利。
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 (XRCCI-77 T/C, Arg 194Trp, Arg28OHis and Arg399Gln; APEI Aspl48Glu; OGG1 Ser326Cys; XPA-4 G/A; XPC PAT: XPD Asp312Asn and Lys75 I Gln) 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 Asp 148Glu 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 XRCCl Arg399Gln and XPD Lys75 I Gln polymorphisms: these polymorphisms were significantly associated with lung cancer in nonsmokers and light smokers (< 25 PY, OR = 4.92, p = 0.021 for XRCCl 399 Gln/Gln; OR = 3.62, p = 0.049 for XPD 751 Gln/Gln), but not in heavy smokers (>= 25 PY; OR = 0.68, p = 0.566 for XRCCl 399 GWGln; OR = 0.46, p = 0.295 for XPD 751 Gln/Gln). Both the XRCCl Arg 194Trp and Arg28OHis 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 XRCCl-77 T/C, the XPA -4 G/A and the XPC PAT polymorphisms. In conclusion, the APEI Aspl48Glu polymorphism is highly predictive for lung cancer, and cumulative cigarette smoking modifies the associations between the XRCCl Arg399Gln and the XPD Lys75 I Gln polymorphisms and lung cancer risk. (c) 2007 Elsevier B.V. All rights reserved.