Zhang Zhi, Miao Xiao-Ping, Tan Wen, Guo Yong-Li, Zhang Xue-Mei, Lin Dong-Xin
Department of Oncologic Radiochemotherapy,Workers' Hospital of Tangshan City, Tangshan, Hebei 063000, P. R. China.
Ai Zheng. 2006 Jan;25(1):7-10.
BACKGROUND & OBJECTIVE: Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are 2 major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT 762Val-->Ala and XRCC1 399Arg-->Gln have been verified to associate with altered protein function and BER activity. This study was to examine the contribution of these 2 polymorphisms, alone or in combination, to the risk of developing gastric cancer.
A total of 236 patients with gastric cancer and 708 cancer-free controls were genotyped for the 2 polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (CI) were calculated using unconditional logistic regression model to evaluate the impact of these 2 polymorphisms on the risk of developing gastric cancer.
The subjects having the ADPRT Ala/Ala genotype had an OR of 2.07 (95% CI=1.33-3.21; P=0.001) compared with those having the Val/Val genotype. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the risk of gastric cancer in a super-multiplicative manner, with an OR of 5.32 (95% CI=1.12-28.57) for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, although the XRCC1 polymorphism itself was not associated with the risk of gastric cancer.
The ADPRT 762Val-->Ala polymorphism plays an important role in the development of gastric cancer, and the XRCC1 399Arg-->Gln polymorphism may serve as a risk modifier.
二磷酸腺苷核糖基转移酶（ADPRT）和X射线修复交叉互补蛋白1（XRCC1）是两种主要的DNA碱基切除修复（BER）蛋白，在刺激和执行BER过程中相互作用。已证实ADPRT 762Val→Ala和XRCC1 399Arg→Gln多态性与蛋白质功能改变和BER活性有关。本研究旨在探讨这两种多态性单独或联合作用对胃癌发生风险的影响。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对236例胃癌患者和708例无癌对照者的这两种多态性进行基因分型。使用非条件逻辑回归模型计算比值比（OR）和95%置信区间（CI），以评估这两种多态性对胃癌发生风险的影响。
与具有Val/Val基因型的受试者相比，具有ADPRT Ala/Ala基因型的受试者的OR为2.07（95%CI=1.33-3.21；P=0.001）。ADPRT和XRCC1多态性的基因-基因相互作用以超相乘的方式增加了胃癌风险，对于同时存在ADPRT 762Ala/Ala和XRCC1 399Gln/Gln基因型的情况，OR为5.32（95%CI=1.12-28.57），尽管XRCC1多态性本身与胃癌风险无关。
ADPRT 762Val→Ala多态性在胃癌发生中起重要作用，而XRCC1 399Arg→Gln多态性可能作为风险修饰因子。
