title: Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity.
abstract: Long non-coding RNA (lncRNA) CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP) rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29-0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30-0.89, p = 0.02, respectively). It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05-2.39, p = 0.03). Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC) subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35-0.98, p = 0.04) and in additive model (adjusted OR = 0.62, 95%CI = 0.43-0.90, p = 0.01). Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36-45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07-3.53, p = 0.03, respectively). Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. hu773589905@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. hu773589905@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Oncology, Changsha Central Hospital, Changsha 410006, China. chenshuhui2008@126.com.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. lvqiaoli2008@126.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. lvqiaoli2008@126.com.
authors.forename: Qiao-Li
authors.initials: QL
authors.lastname: Lv
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. scy_csu2016@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. scy_csu2016@163.com.
authors.forename: Bao
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China. quqiang1983@sina.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Central South University, Zhengzhou 450052, China. qcz0378@126.com.
authors.forename: Chong-Zhen
authors.initials: CZ
authors.lastname: Qin
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. fanlan_038038@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. fanlan_038038@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. guoying881212@csu.edu.cn.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. guoying881212@csu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China. kjade.cheng@hotmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. hhzhou2003@163.com.|Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China. hhzhou2003@163.com.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010984:Platinum; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012737:Sex Factors
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C000605352:CASC8 lncRNA, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D010984:Platinum
keywords: lncRNA CASC8; lung cancer; platinum-based chemotherapy; rs10505477; susceptibility