title: Association between well-characterized lung cancer lncRNA polymorphisms and platinum-based chemotherapy toxicity in Chinese patients with lung cancer.
abstract: Platinum-based chemotherapy is the standard first-line treatment for most lung cancer patients. However, the toxicity induced by platinum-based chemotherapy greatly impedes its clinical use. Previous studies showed that long non-coding RNAs (lncRNAs) with over 200 nucleotides in length affect drug response and toxicity. In the present study, we investigated the association of well-characterized lung cancer lncRNA polymorphisms with platinum-based chemotherapy toxicity in Chinese patients with lung cancer. A total of 467 lung cancer patients treated with platinum-based chemotherapy for at least two cycles were recruited. We primarily focused on gastrointestinal and hematological toxicities. A total of 14 potentially functional polymorphisms within 8 lncRNAs (HOTTIP, HOTAIT, H19, ANRIL, CCAT2, MALAT1, MEG3, and POLR2E) were genotyped. Unconditional logistical regression analysis was conducted to assess the associations. Gene-gene and gene-environment interactions were identified using the software generalized multifactor dimensionality reduction (GMDR). ANRIL rs1333049 was associated with severe overall toxicity in an additive model (adjusted OR=0.723, 95% CI=0.541-0.965, P=0.028). ANRIL rs1333049 was also associated with severe gastrointestinal toxicity in both the additive (adjusted OR=0.690, 95% CI=0.489-0.974, P=0.035) and dominant (adjusted OR=0.558, 95% CI=0.335-0.931, P=0.025) models. MEG3 rs116907618 was associated with severe gastrointestinal toxicity in an additive model (adjusted OR=1.717, 95% CI=1.007-2.927, P=0.047). GMDR identified the three-factor interaction model of POLR2E rs3787016-HOTTIP rs3807598-chemotherapy regimen as the best predictive model for hematological toxicity. In conclusion, ANRIL and MEG3 genetic polymorphisms are associated with severe platinum toxicity and could be considered as biomarkers for pretreatment evaluation in Chinese patients with lung cancer.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.|Hu-nan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Gong
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Peng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Tan
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Di
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University, Hu-nan Key Laboratory of Pharmacogenetics, Changsha 410078, China.|Hu-nan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D044466:Asian People; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D062085:RNA, Long Noncoding; D002945:Cisplatin