PARP-1 Val762Ala polymorphism, CagA+ H-pylori infection and risk for gastric cancer in Han Chinese population
PARP-1 Val762Ala polymorphism, CagA+ H-pylori infection and risk for gastric cancer in Han Chinese population
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DOI：
10.1007/s11033-008-9336-y
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发表时间：
2009-07-01
影响因子：
2.8
通讯作者：
Yuan, Wenzhen
中科院分区：
文献类型：
--
作者：
Zhang, Quanbao;Li, Yumin;Yuan, Wenzhen
PARP-1在碱基切除修复（BER）和基因组完整性的维持中起重要作用。先前的研究发现，PARP-1基因中的Val 762 Ala遗传变异有助于某些癌症的易感性，并降低PARP-1酶活性以应对氧化损伤。幽门螺杆菌（H. pylori）感染被认为是胃癌的主要原因之一。在本研究中，我们研究了PARP-1 Val 762 Ala多态性、CagA（+）H.幽门螺杆菌感染和胃癌的风险。方法采用PCR-RFLP方法对556例胃癌患者（236例胃癌患者和320例无肿瘤及胃肠道疾病的对照组）进行病例对照研究。采用卡方检验和Logistic回归分析计算OR和95%CI。结果762 Ala/Ala基因型在病例组中的检出率（16.9%）高于对照组（10.3%）（OR = 1.942，95%CI = 1.157-3.257，P = 0.011）。多因素分析显示，CagA（+）H等2个因素与胃癌的危险性显著相关。pylori感染（OR为2.562; 95% CI为1.174-5.240，P = 0.037），PARP-1762 AA基因型（OR为1.772; 95% CI为1.065-3.867，P = 0.042）。分层分析表明，Cag（+）H. pylori阳性者中，762 Ala/Ala携带者发生胃癌的危险性高于762瓦尔/瓦尔携带者（OR为2.337; 95% CI为1.148-4.758; P = 0.017）。结论PARP-1762 Ala/Ala可能是中国汉族人群胃癌的危险因素; PARP-1762 Val/Ala多态性和Cag（+）H可能是中国汉族人群胃癌的危险因素。幽门螺杆菌感染共同导致胃癌的高风险。
Introduction PARP-1 plays important role in the BER (base excision repair) and maintenance of genomic integrity. Previous study found the Val762Ala genetic variant in the PARP-1 gene contributed to susceptibility of some cancers and decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter pylori (H. pylori) infection was thought to be one of the major causes of gastric cancer. In this study, we investigated the association between the PARP-1 Val762Ala polymorphism, CagA(+) H. pylori infection, and the risk for gastric cancer. Methods This hospital-based, case-control study was performed involving 556 individuals (236 cases with gastric cancer and 320 controls without evidence of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square test and logistic regression analysis were used to count OR and 95% CI. Results 762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with controls (10.3%), (OR, 1.942; 95% CI, 1.157-3.257, P = 0.011). Multivariate analysis showed that two factors were significantly associated with risk of gastric cancer, including CagA(+) H. pylori infection (OR, 2.562; 95% CI, 1.174-5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065-3.867; P = 0.042). Stratification analysis indicated that among Cag(+) H. pylori positive subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148-4.758; P = 0.017). Conclusion PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han Chinese population; PARP-1 762Val/Ala polymorphism and Cag(+) H. pylori infection jointly contribute to higher risk for gastric cancer.