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Evaluation of miRNA-binding-site SNPs of MRE11A, NBS1, RAD51 and RAD52 involved in HRR pathway genes and risk of breast cancer in China.
- Source :
-
Molecular Genetics & Genomics . Jun2015, Vol. 290 Issue 3, p1141-1153. 13p. - Publication Year :
- 2015
-
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 (OR: 1.87; 95 % CI: 1.23-2.86 and OR: 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 CA decreased the risk of BC (OR: 0.53; 95 % CI: 0.4-0.68), while the TA and TG haplotypes could increase the risk of BC (OR: 1.28; 95 % CI: 1.05-1.57 and OR: 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 = 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16174615
- Volume :
- 290
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Molecular Genetics & Genomics
- Publication Type :
- Academic Journal
- Accession number :
- 102702016
- Full Text :
- https://doi.org/10.1007/s00438-014-0983-5