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

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...

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Autores principales:	Jia-Jia Cui, Lei-Yun Wang, Tao Zhu, Wei-Jing Gong, Hong-Hao Zhou, Zhao-Qian Liu, Ji-Ye Yin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ee2c17defb344cca14b8656b94d58b5
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spelling	oai:doaj.org-article:2ee2c17defb344cca14b8656b94d58b52021-12-02T15:05:39ZGene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients10.1038/s41598-017-05246-82045-2322https://doaj.org/article/2ee2c17defb344cca14b8656b94d58b52017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05246-8https://doaj.org/toc/2045-2322Abstract 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.Jia-Jia CuiLei-Yun WangTao ZhuWei-Jing GongHong-Hao ZhouZhao-Qian LiuJi-Ye YinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jia-Jia Cui Lei-Yun Wang Tao Zhu Wei-Jing Gong Hong-Hao Zhou Zhao-Qian Liu Ji-Ye Yin Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
description	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 × 10−5). 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.
format	article
author	Jia-Jia Cui Lei-Yun Wang Tao Zhu Wei-Jing Gong Hong-Hao Zhou Zhao-Qian Liu Ji-Ye Yin
author_facet	Jia-Jia Cui Lei-Yun Wang Tao Zhu Wei-Jing Gong Hong-Hao Zhou Zhao-Qian Liu Ji-Ye Yin
author_sort	Jia-Jia Cui
title	Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
title_short	Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
title_full	Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
title_fullStr	Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
title_full_unstemmed	Gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
title_sort	gene-gene and gene-environment interactions influence platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2ee2c17defb344cca14b8656b94d58b5
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_version_	1718388755631439872

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

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