title: Genetic Variations in Key MicroRNAs are Associated With the Survival of Nonsmall Cell Lung Cancer.
abstract: MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules involved in carcinogenesis. It has been identified that genetic variations in miRNAs contribute to cancer risk, prognosis, and survival. In the present study, we investigated whether single nucleotide polymorphisms (SNPs) of several key miRNAs (miR-184, miR-218, and miR-124) were associated with the prognosis of nonsmall cell lung cancer (NSCLC) in a clinical cohort study including 1001 cases. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs). We found that 5 SNPs were associated with NSCLC survival (rs919968, rs3775815, rs4867902, and rs6122390 in an additive model: adjusted HR = 1.15, 95% CI = 1.02-1.29; adjusted HR = 0.78, 95% CI = 0.67-0.91, adjusted HR = 1.24, 95% CI = 1.09-1.41; adjusted HR = 1.21, 95% CI = 1.07-1.36, respectively; rs298206 in a dominant model: HR = 1.25, 95% CI = 1.05-1.49). Even after the Bonferroni correction, 3 SNPs remained significant (adjusted P = 0.010, 0.010, and 0.032 for rs3775815, rs4867902, and rs6122390, respectively). Additionally, the combined analysis of these 5 SNPs showed a significant locus-dosage effect between number of unfavorable alleles (rs919968-A, rs3775815-C, rs4867902-G, rs6122390-A, and rs298206-T) and death risk of NSCLC (P for trend < 0.001). A statistically significant multiplicative interaction was found between the genotypes of rs4867902 and surgical operation status (Pint = 0.013). These findings indicated that genetic variations in miRNAs (miR-184, miR-218, and miR-124) might be prognostic markers for NSCLC patients.
authors.affiliation: From the Department of Geriatrics (SW, YL, WX, BC, JW); Editorial Department of Journal of Clinical Dermatology (YP); Department of Oncology, The First Affiliated Hospital of Nanjing Medical University (JX); Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University (WS, MZ, KX, LG, YW, ZH, HM); Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University (WS, MZ, KX, LG, YW, ZH, HM, HS); and State-Level Model Center of Experimental Teaching, Department of Hygienic Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China (SC).
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Yun
authors.initials: Y
authors.lastname: Pan
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Xie
authors.forename: Liguo
authors.initials: L
authors.lastname: Geng
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Jiali
authors.initials: J
authors.lastname: Xu
authors.forename: Songyu
authors.initials: S
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Jianqing
authors.initials: J
authors.lastname: Wu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000368:Aged; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: C509207:MIRN124 microRNA, human; C534424:MIRN184 microRNA, human; C547471:MIRN218 microRNA, human; D035683:MicroRNAs