Gene-gene and Gene-environment Interactions Influence Platinum-based Chemotherapy Response and Toxicity in Non-small Cell Lung Cancer Patients

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jul 13

PMID 28698656

Citations 15

Authors

Jia-Jia Cui

Lei-Yun Wang

Tao Zhu

Wei-Jing Gong

Hong-Hao Zhou

Zhao-Qian Liu

Ji-Ye Yin

Affiliations

Soon will be listed here.

Abstract

Platinum-based chemotherapy is a major therapeutic regimen of lung cancer. Various single nucleotide polymorphisms (SNPs) reported were associated with platinum-based chemotherapy response and drug toxicity. However, neither of the studies explored this association from SNP-SNP interaction perspective nor taking into effects of SNP-environment consideration simultaneously. We genotyped 504 polymorphisms and explore the association of gene-gene and gene-environment interactions with platinum-based chemotherapy response and toxicity in 490 NSCLC patients. 16 SNPs were found significantly associated with platinum-based chemotherapy, and they were picked out as study object in the validation cohort. We recruited 788 patients in the validation cohort. We found that HSPD1 rs17730989-SUMF1 rs2633851 interaction was associated with platinum-based chemotherapy-induced hematologic toxicity (adjusted OR = 0.233, P = 0.018). In addition, the combined effect of ABCG2 rs2231142-CES5A rs3859104 was significantly associated with overall toxicity (adjusted OR = 8.044, P = 4.350 × 10). Besides, the model of ARHGAP26 rs3776332-ERCC6 rs2228528-SLC2A1 rs4658-histology was associated with platinum-based chemotherapeutic response. Gene-gene and gene-environment interactions have been identified to contribute to chemotherapy sensitivity and toxicity. They can potentially predict drug response and toxicity of platinum-based chemotherapy in NSCLC patients.

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