title: Evaluation of miRNA-binding-site SNPs of MRE11A, NBS1, RAD51 and RAD52 involved in HRR pathway genes and risk of breast cancer in China.
abstract: MiRNA-binding-site single nucleotide polymorphisms (SNPs) in homologous recombination repair (HRR) pathway genes may change DNA repair capacity and affect susceptibility to cancer though complex gene-gene and gene-reproductive factors interactions. However, these SNPs associated with breast cancer (BC) are still unclear in Chinese women. Therefore, we conducted a case-control study to evaluate the genetic susceptibility of the five miRNA-binding-site SNPs in HRR pathway genes (MRE11A rs2155209, NBS1 rs2735383, RAD51 rs963917 and rs963918 and RAD52 rs7963551) in the development of BC. MRE11A rs2155209 and RAD52 rs7963551 were found to be associated with BC risk (ORadjusted: 1.87; 95 % CI: 1.23-2.86 and ORadjusted: 0.36; 95 % CI: 0.24-0.58). NBS1 rs2735383, RAD51 rs963917 and rs963918 were associated with BC risk after stratification according to reproductive factors. Haplotypes of Crs963917Ars963918 decreased the risk of BC (ORadjusted: 0.53; 95 % CI: 0.4-0.68), while the Trs963917Ars963918 and Trs963917Grs963918 haplotypes could increase the risk of BC (ORadjusted: 1.28; 95 % CI: 1.05-1.57 and ORadjusted: 1.31; 95 % CI: 1.09-1.62). Combined effect of risk alleles showed that the five SNPs were associated with increased BC risk in a dose-dependent manner (P trend = 0.003). The GC genotype of rs2735383, AG + GG genotype of rs963918 and AC + CC genotype of rs7963551 were associated with PR positivity of BC patients. These findings suggest that the miRNA-binding-site SNPs involved in HRR pathway genes may affect susceptibility of BC in Chinese women; moreover, the interactions of gene-gene and gene-reproductive factors play vital roles in the progression of BC. Further functional studies with larger sample are needed to support and validate these findings.
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, People's Republic of China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Song
authors.forename: Kaijuan
authors.initials: K
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Yan
authors.forename: Jingruo
authors.initials: J
authors.lastname: Li
authors.forename: Liping
authors.initials: L
authors.lastname: Dai
mesh_terms: D000328:Adult; D001665:Binding Sites; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D000076228:MRE11 Homologue Protein; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics*; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics*; D059767:Recombinational DNA Repair; D012306:Risk
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D035683:MicroRNAs; C112156:NBN protein, human; D009687:Nuclear Proteins; C497194:RAD52 protein, human; D051721:Rad52 DNA Repair and Recombination Protein; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000076228:MRE11 Homologue Protein