Variation in the Dicer and RAN Genes Are Associated with Survival in Patients with Hepatocellular Carcinoma.
Single-nucleotide polymorphisms (SNPs) in microRNA machinery genes might affect microRNA processing and subsequently impact tumorigenesis. The aim of this study was to investigate the associations between SNPs in microRNA machinery genes and hepatocellular carcinoma (HCC) in a Korean population. Genotyping of six SNPs in microRNA machinery genes was performed using blood samples from 147 patients with HCC and 209 healthy control subjects. None of the six SNPs in microRNA machinery genes were significantly associated with HCC development. However, among the models for six polymorphic loci-DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) and XPO5 (rs11077)-one allele combination (A-A-T-C-C-C) showed synergistic effects in terms of an increased risk of HCC development (odds ratio = 8.881, 95% confidence interval [CI] = 1.889-41.750; P = 0.002). Multivariate Cox proportional hazard regression analysis showed a significant survival benefit for the DICER rs3742330 GG compared with the AA type (hazard ratio [HR], 0.314; 95% CI, 0.135-0.730; P = 0.007) and for the RAN rs14035 CT compared with the CC genotype (HR, 0.587; 95% CI, 0.349-0.987; P = 0.044). Although we found no direct association between DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) or XPO5 (rs11077) polymorphisms and HCC risk, we demonstrated that DICER (rs3742330) and RAN (rs14035) were associated with the survival of HCC patients. Future studies with larger samples are needed to determine associations of SNPs in microRNA machinery genes with HCC risk and prognosis.
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Mi Na
MN
Kim
Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.|Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.
Jung Oh
JO
Kim
Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Seung Min
SM
Lee
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Hana
H
Park
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Ju Ho
JH
Lee
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Kyu Sung
KS
Rim
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
Seong Gyu
SG
Hwang
Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.|Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.
Nam Keun
NK
Kim
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D028884:Karyopherins / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012044:Regression Analysis; D056910:Republic of Korea; D043244:Ribonuclease III / Q000235:genetics*; D017741:Survivors; D020931:ran GTP-Binding Protein / Q000235:genetics*
D028884:Karyopherins; D035683:MicroRNAs; C120587:RAN protein, human; C446511:XPO5 protein, human; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D020931:ran GTP-Binding Protein