Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110001, PR China.
BMC Cancer. 2009 Dec 15;9:439. doi: 10.1186/1471-2407-9-439.
Excision repair cross-complementing group 1 (ERCC1) and group 2 (ERCC2), and X-ray repair cross-complementing group 1 (XRCC1) proteins play important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence treatment effect and survival of cancer patients. This study aimed to investigate the relationship between polymorphisms in ERCC2, ERCC1 and XRCC1 genes and survival of non-smoking female patients with lung adenocarcinoma.
We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to evaluate SNPs in ERCC2, ERCC1 and XRCC1 genes among 257 patients.
The overall median survival time (MST) was 13.07 months. Increasing numbers of either ERCC1 118 or XRCC1 399 variant alleles were associated with shorter survival of non-smoking female lung adenocarcinoma patients (Log-rank P < 0.001). The adjusted hazard ratios (HRs) for individuals with CT or TT genotype at ERCC1 Asn118Asn were 1.48 and 2.67 compared with those with CC genotype. For polymorphism of XRCC1 399, the HRs were 1.28 and 2.68 for GA and AA genotype. When variant alleles across both polymorphisms were combined to analysis, the increasing number of variant alleles was associated with decreasing overall survival. Using the stepwise Cox regression analysis, we found that the polymorphisms in ERCC1 and XRCC1, tumor stage and chemotherapy or radiotherapy status independently predicted overall survival of non-smoking female patients with lung adenocarcinoma.
Genetic polymorphisms in ERCC1 and XRCC1 genes might be prognostic factors in non-smoking female patients with lung adenocarcinoma.
切除修复交叉互补基因 1（ERCC1）和 2（ERCC2）以及 X 射线修复交叉互补基因 1（XRCC1）蛋白在 DNA 损伤和加合物的修复中发挥重要作用。DNA 修复基因的单核苷酸多态性（SNP）被怀疑会影响癌症患者的治疗效果和生存。本研究旨在探讨 ERCC2、ERCC1 和 XRCC1 基因多态性与非吸烟女性肺腺癌患者生存的关系。
我们使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法评估了 257 例患者 ERCC2、ERCC1 和 XRCC1 基因的 SNP。
总体中位生存时间（MST）为 13.07 个月。非吸烟女性肺腺癌患者中，ERCC1 118 或 XRCC1 399 变异等位基因数量的增加与生存时间缩短相关（对数秩检验 P<0.001）。ERCC1 Asn118Asn 处 CT 或 TT 基因型个体的调整后危险比（HR）分别为 1.48 和 2.67，与 CC 基因型个体相比。对于 XRCC1 399 的多态性，GA 和 AA 基因型的 HR 分别为 1.28 和 2.68。当两个多态性的变异等位基因组合进行分析时，变异等位基因数量的增加与总生存时间的减少相关。使用逐步 Cox 回归分析，我们发现 ERCC1 和 XRCC1 多态性、肿瘤分期以及化疗或放疗状态独立预测了非吸烟女性肺腺癌患者的总体生存。
ERCC1 和 XRCC1 基因的遗传多态性可能是非吸烟女性肺腺癌患者的预后因素。
