Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer.
Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer.
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DOI：
10.18632/oncotarget.8052
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Wei Q
中科院分区：
文献类型：
--
作者：
Jia M;Zhu M;Wang M;Sun M;Qian J;Ding F;Chang J;Wei Q
JNK和P38α通路在基因毒性应激下的组织稳态、细胞凋亡和自噬中起着至关重要的作用，但尚不清楚这些通路中基因的单核苷酸多态性（SNP）是否在晚期非小细胞肺癌（NSCLC）患者中铂类化疗诱导的毒性中起作用。我们对689例接受铂类联合化疗方案治疗的晚期NSCLC患者的JNK和P38α通路中9个基因的11个选定的、独立的、潜在功能性SNP进行了基因分型。在345名患者的发现组中测试了这些SNP与化疗毒性之间的关联，然后在344名患者的复制组中验证。在发现组和验证组及其汇总分析中，GADD 45 B rs2024144 T变异等位基因携带者发生严重血液学毒性的风险显著更高，而MAPK 14 rs3804451 A变异等位基因携带者发生总体毒性和胃肠道毒性的风险显著更高。此外，GADD 45 A rs581000 C携带者贫血的风险较低，而GADD 45 B rs2024144 T携带者白细胞减少症或粒细胞缺乏症的风险显著较高。本研究提供的证据表明，JNK和P38α通路相关基因的遗传变异可能预测晚期NSCLC患者的铂类化疗毒性结局。需要对其他患者人群进行更大规模的研究来验证我们的发现。
The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings.
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影响因子：
21.3
作者：
Papa, S;Zazzeroni, F;Franzoso, G
通讯作者：
Franzoso, G
DOI：
10.1158/1078-0432.ccr-13-0774
发表时间：
2013-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
McWhinney-Glass S;Winham SJ;Hertz DL;Yen Revollo J;Paul J;He Y;Brown R;Motsinger-Reif AA;McLeod HL;Scottish Gynaecological Clinical Trials Group
通讯作者：
Scottish Gynaecological Clinical Trials Group
影响因子：
4.8
作者：
Kovalsky, O;Lung, FDT;Fornace, AJ
通讯作者：
Fornace, AJ
影响因子：
3.7
作者：
Mitra, Sumegha;Wade, Michael S.;Jacobson, Jeffrey R.
通讯作者：
Jacobson, Jeffrey R.
影响因子：
--
作者：
Qiu LX;He J;Cheng L;Zhou F;Wang MY;Sun MH;Zhou XY;Li J;Guo WJ;Wang YN;Yang YJ;Wang JC;Jin L;Zhu XD;Wei QY
通讯作者：
Wei QY