title: Association of a functional RAD52 genetic variant locating in a miRNA binding site with risk of HBV-related hepatocellular carcinoma.
abstract: As an important member in homologous recombination repair, RAD52 plays a crucial part in maintaining genomic stability and prevent carcinogenesis. Several cancer susceptibility RAD52 single nucleotide polymorphisms (SNPs) have been identified previously. However, little or nothing has been known about the RAD52 SNPs and their functional significance in hepatitis B viruses (HBV)-related hepatocellular carcinoma (HCC). Therefore, we investigated the association between five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs7963551, and rs6489769) and HBV-related HCC risk as well as its biological function in vivo. Genotypes were determined in two independent case-control sets from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The allele-specific regulation on RAD52 expression by the functional genetic variant was examined with normal liver tissues. We found that only the RAD52 rs7963551 SNP was significantly associated with HCC risk, with the odds of having the rs7963551 CC genotype in patients was 0.59 (95% CI = 0.45-0.78, P = 1.5 × 10(-4), HCC cases versus chronic HBV carriers) or 0.65 (95% CI = 0.52-0.81, P = 1.1 × 10(-4), HCC cases versus healthy controls) compared with the AA genotype. In the genotype-phenotype correlation analyses of 44 human liver tissue samples, rs7963551 CC or AC was associated with a statistically significant increase of RAD52 mRNA expression, which are consistent to functional relevance of allelic regulation of RAD52 expression by rs7963551 SNP and miRNA let-7 in cancer cells. Our data demonstrated that RAD52 functional rs7963551 SNP contributes to susceptibility to developing HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wei
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Li
authors.affiliation: Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wei
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D002681:China / Q000453:epidemiology; D005260:Female; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051721:Rad52 DNA Repair and Recombination Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein
keywords: Chinese; HBV; HCC; RAD52; genetic polymorphism; susceptibility