title: Associations between genetic variants located in mature microRNAs and risk of lung cancer.
abstract: MiRNAs have been focused for their wide range of biological regulatory functions. Previous studies have suggested that individual miRNAs could influence tumorigenesis through their regulation of specific proto-oncogenes and tumor suppressor genes. This study was implemented to investigate the associations between SNPs in mature microRNAs (miRNAs) and development of lung cancer in a two-stage, case-control study, followed by some functional validations. First, 11 SNPs were analyzed in a case-control study of lung cancer, and the significant results were validated in an additional population. Our results showed that rs3746444 in mir-499 (allele C vs T: OR = 1.33; 95% CI = 1.15-1.54; P = 1.2 × 10-4) and rs4919510 in mir-608 (allele G vs C: OR = 1.27; 95% CI= 1.13-1.43; P = 5.1 × 10-5) were significantly associated with increased risk of lung cancer. Rs3746444 in mir-499 was also significantly associated with poor survival of lung cancer (HR, 1.35; 95% CI, 1.15-1.58; P = 0.0002). The expression levels of mir-499 and mir-608 were significantly lower than those of adjacent normal tissues (P < 0.0005), and the carriers of minor alleles have lower expression levels of mir-499 and mir-608 than those of major alleles (P < 0.001). These findings indicated that rs3746444 in mir-499 and rs4919510 in mir-608 might play a substantial role in the susceptibility to lung cancer.
authors.affiliation: Department of General Internal Medicine, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Dengrui
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pathology, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Clinical Laboratory, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Di
authors.affiliation: Department of Thoracic Surgery, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: The First Department of Oncology, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Second Department of Oncology, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Medical Department, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Chest Hospital of Hebei Province, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, Hebei, China, 050041.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012323:RNA Processing, Post-Transcriptional; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: lung cancer; microRNAs; variant