Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients

• Published in: Scientific reports Vol. 7; no. 1; pp. 5082 - 8
• Main Authors: Cui, Jia-Jia, Wang, Lei-Yun, Zhu, Tao, Gong, Wei-Jing, Zhou, Hong-Hao, Liu, Zhao-Qian, Yin, Ji-Ye
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.07.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 38/61; 45/22; 692/308/53/2423; 692/699/67/1612/1350; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Chemotherapy; Doxorubicin - adverse effects; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Epistasis, Genetic; Female; Gene-Environment Interaction; Genotype-environment interactions; Histology; Humanities and Social Sciences; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; multidisciplinary; Non-small cell lung carcinoma; Platinum; Platinum - adverse effects; Platinum - pharmacology; Platinum - therapeutic use; Reproducibility of Results; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Toxicity
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-05246-8

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 −5 ). 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.