Study On BPCA1 / 2 Mutation In Familial Breast Cancer And Healthy High Risk Population

Background:Recent years,the incidence of breast cancer kept rising,dominating the fist position among much malignant cancer which harms female’s health.As the development of economy,especially in economical developed area of our country or western developed country,pollution of environment is becoming more and more serious and people’s mental press is becoming more and more higher,which harms body seriously and is one of causes leading high incidence of breast cancer. At present,the causes of breast cancer may involve with environment,genetic and hormone factors.Among them,genetic factor may play much more important role.Immediate family members of breast cancer patients may have a higher risk of breast cancer than others.In respect of genetics,mutation of gene is the most common factor.Breast cancer susceptibility gene BRCA1 and BRCA2 had been verified closely related with breast malignant tumor.As a kind of tumor suppressor gene which can encode suppressor proteins,BRCA1/2 gene has an important role in regulating the cell cycle,suppression,activation,transcription,regulation and repair of DNA under normal circumstances,eventually producing negative regulation of tumor cell growth.So BRCA1/2 gene mutations may lead to absence of normal regulation in cell growth,which leads to abnormal cell growth eventually leading to the formation of a tumor.Showed from foreign research about BRCA1/2 gene,these two genes have numerous and various types of mutations even throughout the whole gene. Hot spot of mutations are significantly different between different ethnics and regions and the mutation frequency of Chinese breast cancer patients was significantly lower than the white.To understand the characteristics of mutations of BRCA1/2 gene among Chinese population, several centers in our country screened BRCA1/2 gene mutations among familial breast cancer patients, hoping to discover specific sites,types,spots and regularity of mutations for Chinese people and expecting to establish Chinese population BRCA1 gene mutation spectrum.Some researchers also screened BRCA1/2 gene mutations and evaluated the risk of breast cancer among healthy female relatives of familial breast or ovary cancer patients in foreign country,which showed that the mutation BRCA1/2 gene can enhance higher incidence of breast cancer in the future.But domestic studies of the characteristics of BRCA1/2 gene mutations for the healthy female relatives of familial breast cancer patients haven’t been implemented at present,as well as the studies of assessing risk about breast cancer among people carrying BRCA1/2 gene mutations at high risk.Objective:It had been affirmed that the mutation of breast cancer susceptibility gene BRCA1/2 had close influence on the incidence of familial breast cancer among the white race in Europe and America.However,the Han Chinese’s patterns and sites of mutation of BRCA1/2 gene is significantly different from Europe and America and the trait and law of mutation hasn’t been revealed effectively.Moreover,it is scarce to study the mutation of BRCA1/2 gene and the risk of breast cancer among healthy genetic groups at high risk.For this problem,we designed experiments to study the patterns and characteristic of BRCA1/2 gene mutations among Han Chinese female familial breast cancer patients and healthy genetic groups at high risk.Methods:From December 2013 to October 2014,54 Han Chinese breast cancer patients who were diagnosed in department of Breast Surgery in The People’s Liberation Aarmy 307 Hospital and 24 healthy genetic people at high risk were collected.Detect the coding exons gene sequences of susceptibility gene BRCA1 and BRCA2 by PCR(polymerase chain reaction)-DNA direct sequencing.Results:(1)8 cases of the 54 patients showed pathogenic mutation and the type of them was a single base substitution.The total mutation rate of BRCAland BRCA2 gene was 14.8%,including BRCA1 gene mutation rate,11.1 percentage and BRCA2 gene mutation rate,3.7 percentage.The total mutation rate of BRCA1 gene in Triple Negative Breast Cancer(TNBC) patients was significantly higher than that of Non-triple-negative Breast Cancer(NTNBC) patients(28.6%vsl2.8%),and the difference is statistically significant(P<0.05).(2)2 cases of 24 healthy genetic people at high risk showed BRCAlgene pathogenic mutation and rate of mutation was 8.3%.Conclusion:Through DNA direct sequencing,the gold standard used in detecting mutation of BRCA1/2 gene,we fund that there were mutations of BBRCA1/2 gene among Han Chinese female familial breast cancer patients,contributing the gene mutation spectrum of these groups.In our country,the research of mutation of BRCA1/2 gene about the healthy genetic groups at high risk is almost blank.Through detecting 24 cases of healthy genetic people at high risk, we fund mutations in their BRCA1/2 gene and these mutations is noteworthy because they can help us evaluating the risk of breast cancer among healthy genetic groups at high risk.