Adenosine diphosphate ribosyl transferase and X-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer
Adenosine diphosphate ribosyl transferase and X-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer
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DOI：
10.1053/j.gastro.2006.05.050
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发表时间：
2006-08-01
期刊：
影响因子：
29.4
通讯作者：
Lin, Dongxin
中科院分区：
文献类型：
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作者：
Miao, Xiaoping;Zhang, Xuemei;Lin, Dongxin
背景与目的：腺苷二磷酸核糖基转移酶（ADPRT）和X射线修复交叉互补（XRCC1）是主要的DNA碱基切除修复蛋白，在修复过程中相互作用。本研究检验了 ADPRT Val762Ala 和 XRCC1 Arg399Gln 多态性对 ADPRT-XRCC1 的影响。细胞体外相互作用及其对贲门腺癌（GCA）风险的影响。方法：通过免疫沉淀和免疫印迹分析检查用 ADPRT 和 XRCC1 变异互补 DNA (cDNA) 构建体转染的细胞中 ADPRT-XRCC1 相互作用。对 500 名患者和 1000 名对照者的基因型进行了分析，并通过逻辑回归估计了比值比 (OR)。结果：ADPRT-762Val 与 XRCC1-399Arg 或 XRCC1-399Gln 之间的相互作用很强，但 ADPRT-762Ala 与 XRCC1-399Arg 或 XRCC1-399Gln 之间的相互作用非常弱。病例对照分析显示，与非携带者相比，ADPRT Ala/Ala 或 XRCC:1 Gln/Gln 基因型携带者中 GCA 的 OR 分别为 2.17（95% Cl，1.55-3.04）和 1.61（95% Cl，1.06-2.44）。 ADPRT 和 XRCC1 多态性的基因-基因相互作用以乘法方式增加了 GCA 的 OR（ADPRT Ala/Ala 和 XRCC1 Gln/Gln 基因型同时存在的 OR，6.43；95% Cl，1.80-22.97）。观察到 ADPRT 多态性与吸烟之间的超乘联合效应。对于不吸烟者和吸烟 24 包年的吸烟者，Ala/Ala 基因型的 OR (95% Cls) 分别为 1.44 (0.89-2.32)、2.00 (1.09-3.67) 或 3.19 (1.59-6.42)（P 趋势检验 =.008）。结论：ADPRT 和 XRCC1 多态性赋予宿主对 GCA 的易感性，这可能是由于 ADPRT-XRCC1 相互作用减少和碱基切除修复能力减弱所致。
Background&Aims: Adenosine diphosphate ribosyl transferase (ADPRT) and x-ray repair cross-complementing (XRCC1) are major DNA base excision repair proteins acting interactively in repair processes. This study examined the effects of ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms on ADPRT-XRCC1. interaction in vitro in cells and their contributions to gastric cardia adenocarcinoma (GCA) risk. Methods: The ADPRT-XRCC1 interaction in cells transfected with ADPRT and XRCC1 variant complementary DNA (cDNA) constructs were examined by immunoprecipitation and immunoblotting analysis. Genotypes were analyzed in 500 patients and 1000 controls, and odds ratios (ORs) were estimated by logistic regression. Results: Interactions between ADPRT-762Val and XRCC1-399Arg or XRCC1-399Gln were robust, but interactions between ADPRT-762Ala and either XRCC1-399Arg or XRCC1-399Gln were very weak. A case-control analysis showed ORs of 2.17 (95% Cl, 1.55-3.04) and 1.61 (95% Cl, 1.06-2.44) for GCA in the ADPRT Ala/Ala or XRCC:1 Gln/Gln genotype carriers, respectively, compared with noncarriers. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the OR of GCA in a multiplicative manner (OR for the presence of both ADPRT Ala/Ala and XRCC1 Gln/Gln genotypes, 6.43; 95% Cl, 1.80-22.97). A supermultiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% Cls) of the Ala/Ala genotype for nonsmokers and smokers who smoked 24 pack-years were 1.44 (0.89-2.32), 2.00 (1.09-3.67), or 3.19 (1.59-6.42), respectively (P-trend test =.008). Conclusions: The ADPRT and XRCC1 polymorphisms confer host susceptibility to GCA, which might result from reduced ADPRT-XRCC1 interaction and attenuated base excision repair capacity.