Candidate pathway-based genetic association study of platinum and platinum-taxane related toxicity in a cohort of primary lung cancer patients.
Candidate pathway-based genetic association study of platinum and platinum-taxane related toxicity in a cohort of primary lung cancer patients.
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DOI：
10.1016/j.jns.2014.12.041
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发表时间：
2015-02-15
影响因子：
4.4
通讯作者：
Yang, Ping
中科院分区：
文献类型：
--
作者：
Johnson, Cassandra;Pankratz, Vernon S.;Velazquez, Ana I.;Aakre, Jeremiah A.;Loprinzi, Charles L.;Staff, Nathan P.;Windebank, Anthony J.;Yang, Ping
关键词：
化疗引起的周围神经病变（CIPN）是一种常见的化疗继发毒性。遗传因素可能是使患者易患这种不良反应的重要因素。我们研究了950名原发性肺癌患者，他们接受了铂或铂联合药物化疗，并有DNA可供研究。我们分析了279例CIPN患者和456例非CIPN患者的流行病学危险因素，以及141例CIPN患者和259例非CIPN患者的遗传危险因素。研究的危险因素包括人口统计学、诊断和治疗数据，以及谷胱甘肽、细胞周期、DNA修复、细胞信号传导和凋亡途径中43个候选基因中的174个标签snp（单核苷酸多态性）。糖尿病患者更容易发生CIPN （p=0.0002）。与CIPN相关的其他流行病学危险因素包括周期数（p=0.0004）和同期化疗类型（p<0.001）。与CIPN最相关的snp位于谷胱甘肽过氧化物酶7 （GPX7）基因（p值分别为0.0015和0.0028，未调整和调整）和atp结合盒亚家族C成员4 （ABCC4）基因（p值分别为0.037和0.006，未调整和调整）。我们还发现了甲基-o-鸟嘌呤-甲基转移酶（MGMT）和谷胱甘肽- s -转移酶（GST）异构体的其他暗示关联。该队列中与CIPN相关的流行病学和遗传危险因素包括化疗药物类型、化疗强度以及已知与化疗耐药相关的基因。这些发现表明，区分化疗药物的细胞毒性和神经毒性机制是具有挑战性的，但它代表了个性化治疗和改善患者生活质量的重要一步。
Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity secondary to chemotherapy. Genetic factors may be important in predisposing patients to this adverse effect. We studied 950 primary lung cancer patients, who received platinum or platinum-combination drug chemotherapy and who had DNA available for study. We analyzed epidemiological risk factors in 279 CIPN patients and 456 non-CIPN patients and genetic risk factors in 141 CIPN patients and 259 non-CIPN patients. The risk factors studied included demographic, diagnostic, and treatment data, as well as 174 tag SNPs (single nucleotide polymorphisms) across 43 candidate genes in the glutathione, cell cycle, DNA repair, cell signaling, and apoptosis pathways. Patients who had diabetes mellitus were more likely to have CIPN (p=0.0002). Other epidemiologic risk factors associated with CIPN included number of cycles (p=0.0004) and type of concurrent chemotherapy (p<0.001) . SNPs most associated with CIPN were in glutathione peroxidase 7 (GPX7) gene (p values 0.0015 and 0.0028, unadjusted and adjusted) and in ATP-binding cassette sub-family C member 4 (ABCC4) gene (p values 0.037 and 0.006, unadjusted and adjusted). We also found other suggestive associations in methyl-o-guanine-methyl-transferase (MGMT) and glutathione-S-transferase (GST) isoforms. Epidemiological and genetic risk factors associated with CIPN in this cohort, included the type of chemotherapy drug, intensity of chemotherapy treatment, and genes known to be associated with chemotherapy resistance. These findings suggest that differentiating between cytotoxic and neurotoxic mechanisms of chemotherapy drugs is challenging but represents an important step toward individualized therapy and improving quality of life for patients.
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DOI：
10.1158/1055-9965.epi-09-0871
发表时间：
2010-03
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Moyer AM;Sun Z;Batzler AJ;Li L;Schaid DJ;Yang P;Weinshilboum RM
通讯作者：
Weinshilboum RM
影响因子：
5.3
作者：
Dzagnidze, Anna;Katsarava, Zaza;Thomale, Juergen
通讯作者：
Thomale, Juergen
影响因子：
4.2
作者：
Nurgalieva, Zhannat;Xia, Rui;Du, Xianglin L.
通讯作者：
Du, Xianglin L.
影响因子：
5.7
作者：
Chen, Yen-Chung;Tzeng, Cheng-Hwai;Wang, Wei-Shu
通讯作者：
Wang, Wei-Shu
影响因子：
11.5
作者：
Martin, Lainie P.;Hamilton, Thomas C.;Schilder, Russell J.
通讯作者：
Schilder, Russell J.