title: Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response.
abstract: Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Gong
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
authors.forename: Di
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. lixi6931430@126.com.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China. lixi6931430@126.com.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China. lixi6931430@126.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. liuzhaoqian63@126.com.|Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, People's Republic of China. liuzhaoqian63@126.com.|Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, People's Republic of China. liuzhaoqian63@126.com.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; C561518:CDKN2B antisense RNA, human; C094335:H19 long non-coding RNA; C561566:HOTAIR long untranslated RNA, human; C557041:MALAT1 long non-coding RNA, human; D009944:Organoplatinum Compounds; D062085:RNA, Long Noncoding; C000609264:long non-coding RNA CCAT2, human; C000613830:long noncoding RNA HOTTIP, human
keywords: Long non-coding RNA; Lung cancer; Platinum-based chemotherapy response; Polymorphism; Susceptibility