Molecular Oncology Unit, Portuguese Institute of Oncology, Instituto Português de Oncologia, Laboratórios--Piso 4, R. Dr. Ant. Bernardino Almeida, 4200-072, Porto, Portugal.
Cancer Chemother Pharmacol. 2010 Aug;66(3):501-6. doi: 10.1007/s00280-009-1187-2. Epub 2009 Dec 4.
Lung cancer continues to be the most frequent cancer with approximately one million people worldwide dying of this disease each year. Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. The RAD51 protein is the key protein for homologous recombination, an evolutionarily conserved mechanism for DNA damage repair and the generation of genetic diversity. We conducted this study in order to investigate the effect of the RAD51 G135C polymorphism in treatment response to combined platinum taxanes/gemcitabine first line chemotherapy in NSCLC patients.
We analysed RAD51 G135C polymorphism in 243 NSCLC patients using PCR-RFLP methodology.
There were no statistically significant differences between the groups of NSCLC patients with the different genotypes regarding tumour stage (p = 0.232). Our results indicate that the mean survival rates were statistically different according to the patient's genotypes. The group of patients carrying the C allele presented a higher mean survival rate than the other patients (56.0 months vs. 41.7 months; p = 0.024). Moreover, regarding smoking history, our results demonstrate that overall survival time differed significantly according to the patient's genotypes in smoker and ex-smoker individuals (p = 0.034). No statistically significant differences were found in the genotype frequencies and overall survival rate among non-smoker NSCLC patients (p = 0.413).
This is the first study evaluating the effect of the RAD51 G135C polymorphism in NSCLC patient survival. Our results suggest that RAD51 genotypes could be useful molecular markers for predicting the clinical outcome of NSCLC patients.
肺癌仍然是最常见的癌症，全球每年约有 100 万人死于这种疾病。非小细胞肺癌（NSCLC）约占所有肺癌的 80%。RAD51 蛋白是同源重组的关键蛋白，同源重组是一种进化上保守的 DNA 损伤修复和遗传多样性产生的机制。我们进行这项研究是为了调查 RAD51 G135C 多态性对 NSCLC 患者接受铂类联合紫杉醇/吉西他滨一线化疗治疗反应的影响。
我们使用 PCR-RFLP 方法分析了 243 例 NSCLC 患者的 RAD51 G135C 多态性。
不同基因型 NSCLC 患者的肿瘤分期之间无统计学差异（p = 0.232）。我们的结果表明，根据患者的基因型，平均生存率存在统计学差异。携带 C 等位基因的患者组的平均生存率高于其他患者（56.0 个月比 41.7 个月；p = 0.024）。此外，关于吸烟史，我们的结果表明，在吸烟者和戒烟者中，患者的基因型与总生存时间显著相关（p = 0.034）。在非吸烟者 NSCLC 患者中，基因型频率和总生存率无统计学差异（p = 0.413）。
这是第一项评估 RAD51 G135C 多态性对 NSCLC 患者生存影响的研究。我们的结果表明，RAD51 基因型可能是预测 NSCLC 患者临床结局的有用分子标志物。
