title: Age-related common miRNA polymorphism associated with severe toxicity in lung cancer patients treated with platinum-based chemotherapy.
abstract: Platinum-based chemotherapy toxicity severely impedes successful treatment in lung cancer patients. MicroRNAs (miRs) have a significant impact on the occurrence and survival rate of lung cancer. The purpose of this study was to investigate the association between common miRNA variants and platinum-based chemotherapy toxicity in lung cancer patients. A total of eight functional single nucleotide polymorphisms (SNPs) of miRNA were genotyped in 408 lung cancer patients by MALDI-TOF mass spectrometry. All the patients were histologically confirmed as lung cancer, and were treated with platinum-based chemotherapy for at least two cycles. It was found that the polymorphism rs2042553 of miR-5197 had a significant association with overall severe toxicity in both additive (P=.031, odds ratio [OR]=1.41, 95% confidence interval [CI] 1.03-1.93) and dominant (P=.009, OR=1.80, 95% CI 1.16-2.80) models. MiR-605 rs2043556 was significantly related to severe hepatotoxicity in dominant model (P=.022, OR=2.51, 95% CI 1.12-4.14). In addition, rs2910164 of miR-146a had marginal statistical effect on severe hepatotoxicity in additive model (P=.054). The subgroup analyses showed that miR-27a rs895819 was related to gastrointestinal toxicity in age >56 years old, smoking and non-smoking patients. Taken together, our results revealed that polymorphisms of miR-5197, miR-605, miR-146a, and miR-27a contributed to the chemotherapy toxicity of lung cancer, which may serve as a predictive tool for toxicity evaluation of platinum-based chemotherapy in lung cancer patients.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Gong
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Na-Yiyuan
authors.initials: NY
authors.lastname: Wu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.|Hunan Province Cooperation Innovation Centre for Molecular Target New Drug Study, Hengyang, China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.|Hunan Province Cooperation Innovation Centre for Molecular Target New Drug Study, Hengyang, China.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D016190:Carboplatin / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006402:Hematologic Diseases / Q000139:chemically induced / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C542542:MIRN146 microRNA, human; C531388:MIRN27 microRNA, human; C556602:MIRN605 microRNA, human; D035683:MicroRNAs; D016190:Carboplatin; D002945:Cisplatin
keywords: lung cancer; miRNA; platinum-based chemotherapy; polymorphism; toxicity