LncRNA GAS5 rs145204276 Polymorphism Reduces Renal Cell Carcinoma Susceptibility in Southern Chinese Population

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Xiaoyao Xiang,1 Linfa Chen,2 Jiawen He,3 Guoda Ma,3,4 You Li3 1Department of Urology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 2Department of NeUrology, Huizhou Third People’s Hospital, Guangzhou Medical University, Huizhou, 516000, People’s Republic of China; 3Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 4Maternal and Children’s Health Research Institute, Shunde Maternal and Children’s Hospital, Guangdong Medical University, Shunde, 528300, People’s Republic of ChinaCorrespondence: Guoda Ma, Maternal and Children’s Health Research Institute, Shunde Maternal and Children’s Hospital, Guangdong Medical University, Shunde, 528300, People’s Republic of China, Email sihan1107@126.com You Li, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China, Email youli805@163.comObjective: Recent studies have demonstrated that the long non-coding RNA (lncRNA) GAS5 is closely associated with the onset and progression of several tumor types, including renal cell carcinoma (RCC). This study sought to evaluate the relationship between two functional GAS5 polymorphisms (rs145204276 and rs55829688) and the risk for RCC in the Han Chinese population.Methods: The rs145204276 and rs55829688 polymorphisms in the GAS5 promoter region were genotyped in 624 RCC patients and 655 age/sex-matched healthy participants. The association between these polymorphisms and RCC risk was then evaluated using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Additionally, quantitative RT-PCR was used to determine whether these polymorphisms were associated with changes in the levels of expression of GAS5 in 58 RCC patients.Results: There were significant differences in the GAS5 rs145204276 polymorphism genotype and allele frequencies between the RCC patients and controls (adjusted OR = 0.73, 95% CI = 0.61- 0.87, P = 1.8× 10− 3). When the study participants were stratified based on age, sex, BMI index, and smoking and drinking history, we found that the rs145204276 del allele was associated with a reduced risk for RCC in nondrinkers (P = 3.3× 10− 3), nonsmokers (P = 3.3× 10− 3), females (P = 3.8× 10− 3), and those who were less than 60 years old (P = 3.3× 10− 3). There was also a significant association between the rs145204276 del allele and elevated expression of GAS5 in RCC patients (P = 0.030).Conclusions: The results of this study revealed an association between the rs145204276 polymorphism in the GAS5 lncRNA and the risk for the development of RCC, thus representing a potentially viable biomarker for identifying individuals at risk of developing this form of cancer.Keywords: lncRNA GAS5, polymorphism, renal cell carcinoma, case-control

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