Study On BRCA Mutations Carrying In Breast Cancer Patients Of Chinese Han Nationality In Southern China

ObjectiveAs one of the most common malignant tumors in women, breast cancer stands first on the list of the incidence of malignant tumors among women in China. The incidence also shows a significant uptrend in the world. Therefore, this disease is a malignant disease which has a serious hazard to the physical and mentalhealth among women. The pathogenesis of breast cancer has not yet been entirely clear, and many studies have tended to reveal that the occurrence and development of this disease is caused by genetic mutations and abnormal proliferation of mammary epithelial cells under a combined action of many factors currently. Existing data showed that approximately20%-30%of breast cancer patients had a family history, manifesting as familial carcinoma or hereditary cancer. It is widely believed by researches that Breast Cancer Susceptible gene (BRCA) mutation is an important factor leading to hereditary breast and ovarian cancer syndrome (HBOC). Therefore, it can provide the basis for early prevention and treatment of breast cancer to investigate BRCA mutation carrying and spectrumin breast cancer patients. The present study aims to know BRCA1and BRCA2mutations carrying in breast cancer patients in Southern China through sequencing of all the exons of BRCA1and BRCA2genes, and the mutation testing results can be taken as an important part of BRCA mutation spectrumin hereditary breast cancer patients of Chinese Han nationality, providing the basis and new ideas for related researches and early prevention and treatment of hereditary breast cancer in Chinese.MethodsA total of70breast cancer patients were selected from Guangdong, Hunan, Hubei, Fujian, Guangxi and other provinces and regions in Southern China, including1case with cancer in the bilateral breasts (1.4%),11cases with triple-negative breast cancer (TNBC)(15.7%),6cases with a family history of breast cancer or ovarian cancer (8.6%). Meanwhile,70healthy volunteers were chosen to form the control group (from21provinces including Shandong, Sichuan, Guangdong, Heilongjiang, Henan, Jiangsu, Hunan, Hubei, Hainan, Jilin, etc.). Peripheral venous blood was drawn from all the subjects, and genome DNA was extracted. Gene sequencing was performed for all exons of BRCA1and BRCA2genes by using capture of sequences intarget regions and high-throughput sequencing technology. Finally, BRCA gene mutation carrying in breast cancer patients was analyzed.Results1. A total of5patients (7.14%) were found to carry deleterious mutations of BRCA genes in the study, of them,2cases with BRCA1mutation (2.86%) and3cases with BRCA2mutation (4.29%). And4new deleterious mutations of BRCA genes are detected.2. The detection rate of BRCA gene mutation was related to the family history. The detection rate of BRCA1and BRCA2mutations in patients having a family history was16.67%(1/6). And this rate was markedly higher than the rate of BRCA1and BRCA2gene mutation (P<0.05).3. The patients carrying BRCA mutation were35.2on average. And the patients carrying BRCA1mutation were older than those carrying BRCA2mutation on average (40.5vs31.7, P<0.05).4. In the study,14low-frequency mutations were also found.11of them were classified as suspected benign mutations which may be just low-frequency benign polymorphism. Other3of them were mutations of undetermined significance, these mutations may be associated with genetic susceptibility of breast cancer.5. It was found in the study that several benign polymorphic variations appeared frequently in BRCA1gene and were considered to be the common benign polymorphism of BRCA1gene among Chinese population.6. BRCA1and BRCA2mutation sites can be seen in any place of the genes, and no repetitive sites and high-frequency mutational hotspots were found at present. Otherwise, no patients had both of BRCA1and BRCA2mutations, and no one health person had BRCA mutations.7. The results were all the same with the methods of Sanger (100%).ConclusionsIn the study,4new deleterious mutations of BRCA genes are detected through sequencing of all the exons of BRCA1and BRCA2genes in70breast cancer patients in Southern China, and reported. Meanwhile, some mutations of undetermined significance and benign polymorphisms of BRCA genes are also reported after comparing with70healthy volunteers and analyzing concurrence of mutations and deleterious mutations of BRCA genes, contrast of the mutation frequency between healthy volunteers and patients, coseparation of mutation and disease, and amino acid conservation at mutation sites, etc. The findings of the study enrich the BRCA mutation spectrum in Chinese population and more comprehensively reflect BRCA mutation carrying in Chinese women, providing more bases for early diagnosis and treatment and risk interference.