Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival
Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival
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DOI：
10.1158/0008-5472.can-05-3032
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发表时间：
2006-03-15
期刊：
影响因子：
11.2
通讯作者：
Abbruzzese, JL
中科院分区：
文献类型：
--
作者：
Li, DH;Liu, H;Abbruzzese, JL
DNA修复中的遗传变异可能会影响对细胞毒性疗法的临床反应。我们研究了RecQ 1、RAD 54 L、XRCC 2和XRCC 3基因的6个单核苷酸多态性对378例胰腺癌患者总生存率的影响，这些患者在德克萨斯大学医学博士学位获得者接受治疗。于1999年2月至2004年10月在安德森癌症中心接受随访，并随访至2005年10月。使用MassCode方法确定基因型。从病理诊断到死亡确定生存期。末次随访评价时存活的患者在当时删失。采用Kaplan-Meier曲线、对数秩检验和考克斯回归分析比较不同基因型患者的总生存期。观察到RecQ 1和RAD 54 L基因对所有患者的生存率有显著影响。RecQ 1 159 AA、AC和CC基因型的中位生存时间分别为19.2、14.7和13.2个月，而RAD 54 L 157 CC、CT和TT基因型的中位生存时间分别为16.4、13.3和10.3个月。在亚组分析中，显著降低的生存率与XRCC 2 R188 H和XRCC 3 A17893 G的变异等位基因相关。当这四个基因组合分析时，不利等位基因数量的增加与生存率显著降低相关。亚组分析表明，基因型对生存的影响存在于无转移性疾病的患者或接受放射治疗的患者中。这些观察结果表明，参与DNA双链断裂修复的基因多态性显著影响胰腺癌患者的临床结局。
Genetic variation in DNA repair may affect the clinical response to cytotoxic therapies. We investigated the effect of six single nucleotide polymorphisms of the RecQ1, RAD54L, XRCC2, and XRCC3 genes on overall survival of 378 patients with pancreatic adenocarcinoma,who were treated at University of Texas M.D. Anderson Cancer Center during February 1999 to October 2004 and were followed up to October 2005. Genotypes were determined using the MassCode method. Survival was determined from pathologic diagnosis to death. Patients who were alive at the last follow-up evaluation were censored at that time. Kaplan-Meier plot, log-rank test, and Cox regression were used to compare overall survival by genotypes. A significant effect on survival of all patients was observed for RecQ1 and RAD54L genes. The median survival time was 19.2, 14.7, and 13.2 months for the RecQ1 159 AA, AC, and CC genotypes, and 16.4, 13.3, and 10.3 months for RAD54L 157 CC, CT, and TT genotypes, respectively. A significantly reduced survival was associated with the variant alleles of XRCC2 R188H and XRCC3 A17893G in subgroup analysis. When the four genes were analyzed in combination, an increasing number of adverse alleles were associated with a significantly decreased survival. Subgroup analyses have shown that the genotype effect on survival was present among patients without metastatic disease or among patients who receive radiotherapy. These observations suggest that polymorphisms of genes involved in the repair of DNA doublestrand breaks significantly affect the clinical outcome of patients with pancreatic cancer.