DNA修复基因XRCC1和XPC多态性与胰腺癌风险关联研究

目的探讨碱基切除修复相关基因XRCC1及核酸切除修复基因XPC基因多态与胰腺癌发病风险的关系。方法采用病例-对照研究(胰腺癌新发病例101人,对照337人)方法,分析XRCC1Arg399Gln、Arg194Trp及XPC第9内含子的AT双核苷酸的插入/缺失(PAT)多态与胰腺癌风险的关系。结果经年龄、性别及吸烟、饮酒状态调整后,携带XRCC1399Arg/Gln及Gln/Gln基因型的个体较399Arg/Arg者发生胰腺癌的风险有所降低,OR值分别为0·83(95%CI,0·52~1·34,P=0·41)和0·64(95%CI,0·21~1·66,P=0·30),但没有达到统计学显著水平。携带PAT+/+基因型者发生胰腺癌的风险为XPC/PAT-/-基因型者的0·30倍(95%CI,0·10~0·76,P=0·02)。结论XPC-PAT多态可能在胰腺癌的发生中起着一定的作用。

Polymorphisms of the DNA repair genes XRCC1 and XPC: relationship to pancreatic cancer risk

Objective To determine whether genetic polymorphisms in XRCC1 and XPC are associated with risk of pancreatic cancer. Methods A case-control study was conducted in 101 incident cases with pancreatic cancer and 337 controls (matched for age, sex and ethnicity) to investigate whether genetic polymorphisms in DNA repair genes XRCC1 (Arg194Trp and Arg399Gln) and XPC (an intronic biallelic poly (AT) insertion/deletion polymorphism, XPC-PAT) were associated with risk of pancreatic cancer. The odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by unconditional logistic regression models and adjusted for potential confounding factors. Results There was a small, non-significant decrease in risk for pancreatic cancer in those carrying Gln/Gln genotype at XRCC1 Arg399Gln site (OR 0.64, 95%CI 0.21-1.66, P=0.30) compared with those having Arg/Arg genotypes. And the XRCC1 Arg194Trp polymorphism was not significantly associated with risk of pancreatic cancer. For XPC-PAT polymorphism, 5.0% of cases and 13.4% of controls were homozygous for the variant allele (PAT+/+), resulting in an OR of 0.30 (95%CI 0.10-0.76, P=0.02), which suggested that the PAT+/+ genotype might have protective effect against pancreatic carcinogenesis. Conclusions This study suggest that XPC-PAT polymorphisms may contribute to the risk of pancreatic cancer in our study population.