Association Study Of The Rad51 Gene With Sporadic Breast Cancer In Inner Mongolia

Objective and Background The latest data on global cancer shows that the incidence of breast cancer is increasing year by year,which is the leading cause of cancer death in women^[1].Breast cancer can be divided into two types:familial breast cancer（FBC）based on genetic characteristics and sporadic breast cancer（SBC）,which has no genetic modification.The sporadicity is about 95%.At present,many high-risk genes for breast cancer include breast cancer susceptibility gene 1/2（BRCA1/2）,and BRCA1/2 is a double-strand breaks（DSBs）.The core factor in the post-homologous recombination repair（HRR）^[2]pathway,and multiple pathogenic mutations in the tumor suppressor network with its core composition can damage the integrity and stability of the genome.The prevalence of breast cancer has increased.With the development of genome-wide correlation studies,more key factors in the HRR pathway with BRCA1/2 germline as the core were detected.Rad51 recombinase,as a core participant in homologous recombination,can alter the ability of homologous recombination repair when the Rad51 family is overexpressed or there is a mutation in the Rad51 family,resulting in instability of the entire genome and induction of cancer^[3].Therefore,the detection of the Rad51 family,found that its mutations and abnormal expression,is expected to become a new method for breast cancer screening and diagnosis,a new target for treatment and a new indicator of prognosis.Rad51 was first discovered by ogawaH et al in 1993,and then a series of studies by foreign research groups,but mainly focused on the exploration of FBC,and reported little on SBC.Foreign scholars have found that the Rad51 gene in breast cancer has different susceptibility in different regions and different populations.The mutation rate of Rad51 in Europeans is significantly higher than that in other regions and populations^[4].However,there is little research on the Rad51 gene in different ethnic groups in the same region.Therefore,it is necessary to compare the genetic susceptibility and expression distribution of Rad51 gene in Mongolian and Han nationality SBC in Inner Mongolia,and explore its polymorphism and expression with Inner Mongolia.The association of clinical pathological indicators of breast cancer in the region,in order to actively explore the formation process and pathogenesis of SBC,has a certain potential for individualized screening,treatment and prognosis of high-risk groups.In this study,Rad51 gene rs963917and rs1801320 were used to investigate the genetic susceptibility of breast cancer in Mongolian and Han women in Inner Mongolia.Method（1）From January 2017 to May 2018,80 patients with SBC who had a clear pathological diagnosis after surgical resection of Inner Mongolia Medical University Hospital were selected,and the clinical data were complete.Forty Mongolian and Han nationality were randomly selected.Twenty patients with breast fibroadenoma of Han and Han nationality were used as controls.The expression of Rad51gene in Mongolian and Han nationality SBC in Inner Mongolia was analyzed by immunohistochemistry.The potential relationship between Rad51 gene expression and clinical pathological parameters of SBC in Inner Mongolia was discussed.（2）EDTA（Ethylene Diamine Tetraacetic Acid）anticoagulant vacuum blood collection tube was used to extract 86 cases of SBC patients（ie,case group:50 cases of Han nationality,36 cases of Mongolian）and the health of the medical examination center during the same period.86women（control group:50 cases of Han nationality,36 cases of Mongolian）2ml of peripheral venous blood,shocked and mixed and numbered,frozen in-80°C refrigerator.After extracting nuclear DNA,PCR（Poltmerase Chain Reaction）and direct sequencing method were used to analyze whether the polymorphisms of Rad51 gene rs1801320 and rs963917were different in Mongolian and Han women’s SBC,and they were related to SBC in Inner Mongolia.The potential correlation between clinical pathological indicators;Logistic regression model was used to analyze the OR value and 95%CI,and the relationship between different genotypes and alleles and the risk of SBC in Inner Mongolia was compared.Results（1）The subcellular localization of Rad51 in Mongolian and Han SBC is located in the cytoplasm.The positive expression rate of Rad51 in cancer tissues is 42.5%（34/80）,and the positive expression rate of Rad51 in breast fibroadenoma tissues is 12.5%??（5/40）,there was a statistically significant difference between the two groups（P<0.01）.（2）The positive expression rate of Rad51 in Mongolian SBC tissues was 40%（16/40）,and the positive expression in 20 cases of breast fibroadenomas was 10%（2/20）.The difference was statistically significant（P<0.05）;the positive expression rate of Rad51 in 40 Han Chinese breast cancer tissues was 45%（18/40）,while the positive expression rate in 20 cases of breast fibroadenoma was 15%（3/20）.Statistical significance（P<0.05）.The positive expression of Rad51 was not statistically significant in Mongolian and Han SBC tissues（P>0.05）.（3）The expression of Rad51 in Mongolian SBC tissues was associated with lymph node invasion,tumor differentiation,and TNM staging（P<0.05）.Han SBC was associated with tumor differentiation and TNM staging（P<0.05）.There was no significant difference in age,tumor diameter,steroid status,HER-2 and Ki-67 proliferation（P>0.05）.（4）Rad51 rs1301320 and rs963917 can detect three genotypes in Mongolian and Han nationality SBC,namely GG,GC,CC and TT,TC and CC.（5）The genotypes and alleles of Rad51 rs1301320 and rs963917were not significantly different between Mongolian and Han（P>0.05）.（6）The genotype distribution of rs1301320 in SBC patients in Inner Mongolia was statistically significant in ER status and TNM stage;while the genotype distribution of rs963917 was only significantly different in ER status（P<0.01）;There were no significant clinical and pathological parameters such as age,mass diameter,lymph node involvement,PR status,HER-2,Ki-67 proliferation and tumor differentiation（P>0.05）.（7）Compared with GG,rs1301320 in SBC patients in Inner Mongolia can increase the risk of breast cancer（OR=1.382,95%CI=1.112¹.694,P<0.05）;rs963917 allele C and T phase Compared,it can reduce the risk of breast cancer（OR=0.804,95%CI=0.691⁰.917,P<0.05）.Conclusions（1）Rad51 positive staining is located in the cytoplasm and is highly expressed in cancer cells,and there is no differential expression in Mongolian and Han female SBC.（2）The high expression of Rad51 gene may be related to the TNM stage of Mongolian SBC,the degree of differentiation of cancer tissues and the invasion of lymph nodes;it is related to the clinical stage of Han Chinese SBC and the degree of differentiation of cancer tissues.（3）The high expression of Rad51 gene may be related to the prognosis of SBC in Inner Mongolia,but further research is needed to further expand the sample size combined with other detection methods and related genes.（4）The distribution of Rad51rs1301320 and rs963917 genotypes was not detected in Mongolian and Han SBC tissues.（5）Rad51 rs1301320 site CC genotype carriers have increased risk of breast cancer,CC genotype may be related to clinical stage and ER status of SBC;Rad51 rs963917site C allele may reduce the risk of breast cancer,TT genotype carriers are relatively highly distributed in ER（-）breast cancer.