Abstract 2777: Evaluation of miRNA-binding-site SNPs of MRE11A, NBS1, RAD51 and RAD52 in HRR pathway genes and risk of breast cancer in China

BACKGROUND: MiRNA-binding-site single nucleotide polymorphisms (SNPs) in homologous recombination repair (HRR) pathway genes may change DNA repair capacity and affect susceptibility to cancer. However, these SNPs associated with breast cancer (BC) are still unclear in Chinese women. METHODS: We performed a case-control study of 450 BC patients and 450 matched cancer-free controls in Chinese Han women. Five miRNA-binding-site SNPs in HRR pathway genes (MRE11A rs2155209, NBS1 rs2735383, RAD51 rs963917 and rs963918 and RAD52 rs7963551) were genotyped by the restriction fragment-length polymorphism (PCR-RFLP) method; a chi-square (χ2) test was used to compare the differences in the genotypic distribution between the BC cases and controls. The interactions of gene-gene and gene-reproduction factors were computed by logistic regression models. RESULTS: Gene-gene and gene-reproduction factors interaction analysis among HRR pathway genes showed significant effects on BC risk. the individuals with TC (OR: 1.87; 95% CI: 1.23-2.86) and TC+CC (OR: 1.86; 95% CI: 1.23-2.80) genotypes of rs2155209 in MRE11A showed increased risk to BC compared with TT genotype after adjustment for age, age at menarche and menopause, menopausal status, number of pregnancy and abortion, breast-feeding status, family history of BC in first-degree relatives. Compared with AA genotype, patients with AC, CC and AC+CC genotype of rs7963551 in RAD52 had a significantly lower risk for BC [OR (95%CI) as 0.67 (0.48, 0.87), 0.36 (0.24, 0.58) and 0.71 (0.59, 0.82), respectively]. Haplotypes of Crs963917Ars963918 decreased the risk of BC (OR: 0.53; 95%CI: 0.41-0.68), while the Trs963917Ars963918 and Trs963917Grs963918 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 breast cancer risk in a dose-dependent manner (Ptrend = 0.003). The GC genotype of rs2735383, AG+GG genotype of rs963918 and AC+CC genotype of rs7963551 were associated with PR positive of BC patients. And among the stratified analysis, no heterogeneity was observed in any strata of the subgroups. CONCLUSION: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-reproduction factors play vital roles in the progression on BC. Further functional studies are needed to validate our results. Citation Format: Chunhua Song, Kaijuan Wang, Zhenzhen Wu, Ye Hua, Peng Wang, Yong Hong Zheng, Xiaoqin Cao, Songyuan Deng. Evaluation of miRNA-binding-site SNPs of MRE11A, NBS1, RAD51 and RAD52 in HRR pathway genes and risk of breast cancer in China. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2777. doi:10.1158/1538-7445.AM2015-2777