Genetic variations in the flanking regions of miR-101-2 are associated with increased risk of breast cancer.
Genetic variants in human microRNA (miRNA) genes may alter mature miRNA processing and/or target selection, and likely contribute to cancer susceptibility and disease progression. Previous studies have suggested that miR-101 may play important roles in the development of cancer by regulating key tumor-associated genes. However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in breast cancer susceptibility remains unclear. In this study, we genotyped 11 SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study of 1064 breast cancer cases and 1073 cancer-free controls. The results revealed that rs462480 and rs1053872 in the flank regions of pre-miR-101-2 were significantly associated with increased risk of breast cancer (rs462480 AC/CC vs AA: adjusted OR = 1.182, 95% CI: 1.030-1.357, P = 0.017; rs1053872 CG/GG vs CC: adjusted OR = 1.179, 95% CI: 1.040-1.337, P = 0.010). However, the remaining 9 SNPs were not significantly associated with risk of breast cancer. Additionally, combined analysis of the two high-risk SNPs revealed that subjects carrying the variant genotypes of rs462480 and rs1053872 had increased risk of breast cancer in a dose-response manner (P(trend) = 0.002). Compared with individuals with "0-1" risk allele, those carrying "2-4" risk alleles had 1.29-fold risk of breast cancer. In conclusion, these findings suggested that the SNPs rs462480 and rs1053872 residing in miR-101-2 gene may have a solid impact on genetic susceptibility to breast cancer, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.
MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Jiaping
J
Chen
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Zhenzhen
Z
Qin
MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Yue
Y
Jiang
Department of Medical Oncology, Jinling Hospital, Southern Medical University, Nanjing, China.
Yanru
Y
Wang
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Yisha
Y
He
MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Juncheng
J
Dai
MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China ; Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Guangfu
G
Jin
MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China ; Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Hongxia
H
Ma
MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China ; Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Zhibin
Z
Hu
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yongmei
Y
Yin
MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China ; Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Hongbing
H
Shen
D024509:3' Flanking Region; D024506:5' Flanking Region; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
C534072:MIRN101 microRNA, human; D035683:MicroRNAs