Genetic variants in regulatory regions of microRNAs are associated with lung cancer risk
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Kaipeng Xie1,2,*, Cheng Wang1,2,*, Na Qin1,2, Jianshui Yang1,2, Meng Zhu1,2, Juncheng Dai1,2, Guangfu Jin1,2, Hongbing Shen1,2, Hongxia Ma1,2, Zhibin Hu1,2
1Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
2Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, 211166, China
*These authors contributed equally to this work
Zhibin Hu, email: [email protected]
Hongxia Ma, email: [email protected]
Keywords: non-small cell lung cancer, microRNA, susceptibility, survival
Received: February 18, 2016 Accepted: May 28, 2016 Published: June 25, 2016
Genetic variants in regulatory regions of some miRNAs might be associated with lung cancer risk and survival. We performed a case-control study including 1341 non-small cell lung cancer (NSCLC) cases and 1982 controls to evaluate the associations of 7 potentially functional polymorphisms in several differently expressed miRNAs with NSCLC risk. Each SNP was also tested for the association with overall survival of 1001 NSCLC patients. We identified that rs9660710 in miR-200b/200a/429 cluster and rs763354 in miR-30a were significantly associated with NSCLC risk [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.06–1.30, P = 0.002; OR = 0.88, 95% CI = 0.80–0.98, P = 0.017; respectively]. However, no significant association between variants and NSCLC death risk was observed in survival analysis. Functional annotation showed that both rs9660710 and rs763354 were located in regulatory elements in lung cancer cells. Compared to normal tissues, miR-200a-3p, miR-200a-5p, miR-200b-3p, miR-200b-5p and miR-429 were significantly increased in The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma (LUAD) tumors, whereas miR-30a-3p and miR-30a-5p were significantly decreased in tumors (all P < 0.05). Furthermore, we observed that rs9660710 is an expression quantitative trait locus (eQTL) or methylation eQTL for miR-429 expression in TCGA normal tissues. Our results indicated that rs9660710 in miR-200b/200a/429 cluster and rs763354 in miR-30a might modify the susceptibility to NSCLC.
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