Genetic polymorphism in ATIC is associated with effectiveness and toxicity of pemetrexed in non-small-cell lung cancer

被引：8

作者：

Visser, Sabine ^{[1
,2
,3
]}

Koolen, Stijn ^{[4
,5
]}

van Donk, Nadine ^{[6
]}

van Walree, Nico ^{[2
]}

van der Leest, Cor ^{[2
]}

Cornelissen, Robin ^{[1
]}

van Schaik, Ron ^{[6
]}

Mathijssen, Ron ^{[4
]}

Aerts, Joachim ^{[1
]}

Stricker, Bruno H. ^{[3
,7
]}

机构：

[1] Erasmus MC, Dept Pulm Med, Canc Inst, Rotterdam, Netherlands

[2] Amphia Hosp, Dept Pulm Med, Breda, Netherlands

[3] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[4] Erasmus MC, Dept Med Oncol, Canc Inst, Rotterdam, Netherlands

[5] Erasmus MC, Dept Hosp Pharm, Rotterdam, Netherlands

[6] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands

[7] Netherlands Healthcare Inspectorate, Utrecht, Netherlands

来源：

THORAX | 2021年 / 76卷 / 11期

关键词：

lung cancer chemotherapy; lung cancer; clinical epidemiology; non-small cell lung cancer; THERAPY;

D O I：

10.1136/thoraxjnl-2020-216504

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Patients with advanced non-small-cell lung cancer who are treated with pemetrexed display a wide variation in clinical response and toxicity. In this prospective, multicentre cohort study, we investigated the association with treatment effectiveness and toxicity of 10 polymorphisms in nine candidate genes, covering the folate pathway (MTHFR), cell transport (SLC19A1/ABCC2/ABCC4), intracellular metabolism (FPGS/GGH) and target enzymes (TYMS/DHFR/ATIC) of pemetrexed. Adjusted for sex, ECOG performance score and disease stage, the association between ATIC (rs12995526) and overall survival (HR 1.59, 95% CI 1.06 to 2.39) was significant. Regarding toxicity, this ATIC polymorphism was significantly associated with severe laboratory (p=0.014) and clinical (p=0.016) chemotherapy-related adverse events, severe neutropenia (p=0.007) and all-grade diarrhoea (p=0.034) in multivariable analyses.

引用

页码：1150 / 1153

页数：4

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