Genetic variations in the regulator of G-protein signaling genes are associated with survival in late-stage non-small cell lung cancer.
Genetic variations in the regulator of G-protein signaling genes are associated with survival in late-stage non-small cell lung cancer.
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DOI：
10.1371/journal.pone.0021120
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Dai J;Gu J;Lu C;Lin J;Stewart D;Chang D;Roth JA;Wu X
G蛋白信号通路调节因子（Regulator of G-protein signaling，RGS）在信号转导、细胞活动和肿瘤发生中起着重要作用。我们推测RGS基因家族的遗传变异可能与晚期非小细胞肺癌（NSCLC）患者对化疗或放化疗的反应有关。我们选择了17个RGS基因中的95个标记单核苷酸多态性（SNP），并在598例晚期NSCLC患者中进行基因分型。13个SNP与总生存率显著相关。其中，RGS 12的rs 2749786最显著。通过化疗或放化疗的分层分析进一步确定了与亚组总生存率相关的SNP。RGS 1的rs 2816312和RGS 7的rs6689169分别在化疗组和放化疗组中最显著。当这些SNP组合时，观察到显著的累积效应。生存树分析确定了rs 944343、rs 2816312和rs 1122794之间影响化疗患者生存时间的潜在相互作用，而rs6429264的基因型影响放化疗患者的生存。据我们所知，这是第一个研究，以揭示RGS基因家族在晚期NSCLC患者的生存的重要性。
The regulator of G-protein signaling (RGS) pathway plays an important role in signaling transduction, cellular activities, and carcinogenesis. We hypothesized that genetic variations in RGS gene family may be associated with the response of late-stage non-small cell lung cancer (NSCLC) patients to chemotherapy or chemoradiotherapy. We selected 95 tagging single nucleotide polymorphisms (SNPs) in 17 RGS genes and genotyped them in 598 late-stage NSCLC patients. Thirteen SNPs were significantly associated with overall survival. Among them, rs2749786 of RGS12 was most significant. Stratified analysis by chemotherapy or chemoradiation further identified SNPs that were associated with overall survival in subgroups. Rs2816312 of RGS1 and rs6689169 of RGS7 were most significant in chemotherapy group and chemoradiotherapy group, respectively. A significant cumulative effect was observed when these SNPs were combined. Survival tree analyses identified potential interactions between rs944343, rs2816312, and rs1122794 in affecting survival time in patients treated with chemotherapy, while the genotype of rs6429264 affected survival in chemoradiation-treated patients. To our knowledge, this is the first study to reveal the importance of RGS gene family in the survival of late-stage NSCLC patients.
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