Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer.
Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer.
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DOI：
10.1097/mpa.0b013e31821268d1
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发表时间：
2011-07
期刊：
影响因子：
2.9
通讯作者：
Risch HA
中科院分区：
文献类型：
--
作者：
Zeng H;Yu H;Lu L;Jain D;Kidd MS;Saif MW;Chanock SJ;Hartge P;PanScan Consortium;Risch HA
生殖系基因变异可能会影响癌症患者的临床结局。我们应用候选基因方法来评估可能的标记物对胰腺癌患者生存的影响。我们还研究了基因-放射治疗和基因-化疗的相互作用，旨在解释治疗结果的个体差异。在一项基于人群的研究中，总共招募了211名胰腺癌患者。从现有的出版物中选择了64个与癌症存活率或治疗反应相关的候选基因。基因分型信息来自以前的GWAs数据集。用比例风险回归模型检验遗传变异和基因特异性治疗交互作用对总生存率的主要影响。14个基因显示出与胰腺癌存活率相关的证据。其中位于DPYD基因的rs1760217、位于SERPINA3的rs17091162和位于ABCG2的rs2231164的P值最低，分别为10−4.60、0.0013和0.0023。我们还观察到两个基因RRM1和IQGAP2与放疗有显著的交互作用，与生存相关，另外两个基因Tyms和Met分别与5-FU和厄洛替尼相互作用。我们的研究表明，在胰腺癌患者中，生殖系基因多态与总存活率之间存在显著的相关性，以及各种基因与放疗和化疗之间的生存交互作用。
Germline genetic variation may affect clinical outcomes of cancer patients. We applied a candidate-gene approach to evaluate the effect of putative markers on survival of patients with pancreatic cancer. We also examined gene-radiotherapy and gene-chemotherapy interactions, aiming to explain inter-individual differences in treatment outcomes. In total, 211 patients with pancreatic cancer were recruited in a population-based study. Sixty-four candidate genes associated with cancer survival or treatment response were selected from existing publications. Genotype information was obtained from a previous GWAS dataset. The main effect of genetic variation and gene-specific treatment interactions on overall survival were examined by proportional hazards regression models. Fourteen genes showed evidence of association with pancreatic cancer survival. Among these, rs1760217, located at the DPYD gene, rs17091162 at SERPINA3 and rs2231164 at ABCG2 had the lowest P-values of 10−4.60, 0.0013 and 0.0023, respectively. We also observed that two genes, RRM1 and IQGAP2, had significant interactions with radiotherapy in association with survival, and two others, TYMS and MET, showed evidence of interaction with 5-FU and erlotinib, respectively. Our study suggested significant associations between germline genetic polymorphisms and overall survival in pancreatic cancer, as well as survival interactions between various genes and radiotherapy and chemotherapy.