| Objective : For Chinese women,breast cancer has become the most common malignant tumor,of which about 5%~10% are familial breast cancer with genetic susceptibility.Through the investigation and analysis of the family history of breast cancer patients,this study finds out the family genetic breast cancer patients and their family members,conducts the epidemiological investigation of breast cancer risk factors,and tests the mutation of breast cancer susceptibility genes.To obtain comprehensive data of inherited breast cancer susceptibility genes in China,discuss the clinical significance of the detection of tumor susceptibility gene mutation in the high-risk population of breast cancer in China.In order to improve the level of monitoring and prevention of high-risk groups,to provide a basis for the prevention and intervention of breast cancer,so as to develop suitable for the Chinese population genetic testing strategy and carry out genetic counseling work for breast cancer laid the foundation.Methods:1.A total of 91 samples were collected from 23 Chinese familial clustered breast cancer families admitted to the Second Department of Tianjin Medical University Cancer Institute and Hospital from January 2017 to January 2019.2.Complete clinicopathological data of 28 cases of breast cancer diagnosed and treated in Tianjin Medical University Cancer Institute and Hospital were collected.3.Collected 91 cases of peripheral venous blood samples and extract the genomic DNA samples,using the second generation sequencing platform Ion Torrent S5 ?,designed and adopted more than 108 cancer related gene sequencing a panel of 91 samples of sequencing,DNA damage repair are emphatically analyzed related gene mutations,at the same time use the embryo is a mutation SPSS22.0 software to filter out with clinical pathological data of patients with breast cancer and epidemiological characteristics of statistical analysis,with P < 0.05 as the difference was statistically significant.Results:1.Through the analysis of the sequencing data of 91 samples,80 high-quality mutations were selected to occur in 26 genes.A total of 23 BRCA1/2 gene mutation sites(including 9 pathogenic mutations and 14 VUS mutations)and 57 non-BRCA gene mutation sites(including 17 pathogenic mutations and 40 VUS mutations)were found.2.Among the 91 samples,76 were carrying mutations(83.5% carry mutations),which carry the BRCA gene 37 cases,carry the BRCA gene 71 cases,in which 32cases(42.1%,32/76)samples at the same time carry the BRCA and the BRCA mutations,prompt BRCA and join the BRCA mutations of phenomenon is very common in the family hereditary breast cancer.3.Among the BRCA mutated samples,there were 13 cases of BRCA1 gene mutation and 29 cases of BRCA2 gene mutation,among which 5 cases had both BRCA1 and BRCA2 gene mutation.This study found that in Chinese familial breast cancer families,the frequency of BRCA2 mutations is 2.12 times higher than that of BRCA1 mutations.4.In the 91 samples,there were significant differences in ethnic groups between the group with and without genetic mutation(P<0.05),and the genetic mutation was more detected in han females.Those with BRCA gene mutation were more likely to have abortion than those without mutation.There were differences between the non-BRCA mutation group and without genetic mutation,the non-BRCA mutation group also have the history of benign breast disease and the family history of thyroid disease(P<0.05).5.In the sample of 91 cases,there were significant differences between breast cancer patients and healthy family members in weekly exercise time and daily nighttime sleep time(P<0.05).Furthermore,the 91 samples were divided into two subgroups:the group with and without the mutation of the susceptibility gene.It was found that in the group with the mutation of the susceptibility gene,there were still significant differences between the breast cancer patients and their family members in the time of weekly exercise and the time of daily night sleep(P<0.05).No significant statistical difference was found in the group without the gene mutation.6.In 28 breast cancer patients with complete clinical and pathological data,compared with those with negative mutation,BRCA gene mutation patients had higher regional lymph node metastasis rate(P=0.029)and higher TNM stage(P=0.043).Non-BRCA mutants were more likely to be associated with benign breast disease than non-brca mutants(P=0.046).Conclusion:1.This study once again proves that BRCA1/2 gene plays a very important role in the genetic risk of breast cancer,and the role of other genes besides BRCA in the genetic risk of breast cancer cannot be ignored.In this study,BRCA gene detection and DNA damage repair gene detection were carried out simultaneously in the familial inherited breast cancer pedigree,which could increase the detection rate of carriers of pathogenic germline mutations.Therefore,it is necessary to carry out the expanded detection of other breast cancer susceptibility genes besides BRCA in the appropriate population2.Through this study,some new tumor-susceptible gene mutations were found,which further expanded the germline mutation spectrum of familial inherited breast cancer susceptibility genes.However,the clinical significance of most non-BRCA gene mutations was unknown,and it was necessary to carry out targeted functional experiments to clarify its pathogenicity in the future.3.People with non-BRCA gene mutations may be more prone to benign breast diseases,and benign breast diseases are an important risk factor affecting the occurrence of breast cancer.Therefore,non-BRCA gene testing in benign breast patients with a family history will help improve early diagnosis and treatment of breast cancer.4.Breast cancer patients with BRCA gene mutation are more likely to have lymph node metastasis and have higher TNM stage,indicating that BRCA-positive breast cancer is more invasive.Therefore,more perfect treatment plans should be developed for patients with BRCA gene mutation and strict follow-up should be conducted to maximize the survival rate of patients.5.For individuals at high risk of breast cancer who carry tumor-susceptible gene mutation,enhancing physical exercise and ensuring adequate sleep time can help reduce the risk of breast cancer and reduce the occurrence of breast cancer. |
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