Mutation Screening Analysis Of BRCA1/2 Gene In 116 Cases Of High Risk Population

Background:In recent years, the increasing incidence of breast cancer has become the most common malignant tumor that harms female’s health. In 2015, the new cases of female breast cancer patients in China accounted for 15% of all female malignant tumors patients, which stayed at the top of the ranking list. The deaths of breast cancer patients accounted for 7% of the deaths of all female malignant tumors. The etiology of breast cancer is multi-aspect interaction, including environmental and genetic factors, and genetic factors play an important role, the family which has a history of breast cancer will relatively increase the risk of having breast cancer. The risk of women whose mother has ever been diagnosed with breast cancer before the age of 50 is about 1.7 times compared with women without a family history, according to a health study. Among the genetic factors, the BRCA1/2 gene mutation makes the morbidness risk of breast cancer up to 50%-85%. BRCA1/2 gene is a tumor suppressor gene, which is involved in the regulation of DNA damage’s repair and transcription. But BRCA1/2 gene mutation will lose the cycle regulation of DNA damaged cells, causing abnormal growth of cell, and ultimately lead to the occurrence of tumor. Studies have shown that BRCA1/2 gene can occur in many forms of multi-locus gene mutation, and the hot spots of different races, different regions are different, too. In order to findout BRCA1/2 gene mutation and mutation type, hot mutation spot and mutation rules of Chinese population, and to establish BRCA1/2 mutation spectrum of Chinese population, China carried out mutation screening of familial breast cancer patients with BRCA1/2. However, the study of the BRCA1/2 gene mutation characteristics of health risk population, as well as the risk assessment of breast cancer in high-risk carriers of BRCA1/2 gene mutation is still almost blank in the country so far.Objective:BRCA1/2 gene mutation is closely related to the incidence of breast cancer in European and American population. However, compared with the European and American populations, the characteristics of BRCA1/2 mutation in Chinese population are significantly different, and the gene mutation law is not exactly reported. Especially for health high-risk population, the characteristics of BRCA1/2 gene mutation and the risk of breast cancer may occur in the future is even more rare. To solve this problem, we designed this study to analyse the characteristics of BRCA1/2 mutation in 116 cases of health high risk population.Methods:Collect 116 cases of high risk population in Beijing Hehe Medicine Laboratory as the object of study that from January 2015 to October 2015, extract human blood genomic DNA from peripheral blood and use PCR sequencing method detect regional hot spots of BRCA1 exon 2, 11 and 20 and BRCA2 exon 11. Count the ages of cancer diagnosis of the 116 cases’ closest relatives(or confirmed as BRCA1 / BRCA2 mutation carriers), group the population by using 35 years old as the boundary line, compare the mutation rate of BRCA1/2 between the two groups.Results:1、12 cases of pathogenic mutation was found in the 116 cases of high-risk groups, the types of the mutations are missense and all mutations are located on the exon 11.The total mutation rate was 10.3%(12/116),and the BRCA1 mutation rate was 7.7%(9/116), the BRCA2 mutation rate was 3.4%(4/116)(P>0.05).2、There are 28 individuals whose relatives’ age of diagnosis are not less than or equal to 35 years old in the 116 cases. In these 28 people, the total mutation rate of BRCA1/2 was 10.7%,and the BRCA1 mutation rate was 7.1%, as same as the BRCA2 mutation rate. There are 88 individuals whose relatives’ age of diagnosis are more than 35 years old, the total mutation rate of BRCA1/2 was 10.2%, the mutation rates of BRCA1 and BRCA2 are 7.9% and 2.3% respectively. There was no significant difference between the two groups(P>0.05), including the total mutation rate, the mutation rate of BRCA1 gene and the mutation rate of BRCA2 gene.Conclusion:In this paper, PCR sequencing method is used to detect the mutation of BRCA1/2 gene in 116 cases of health high risk population. The result shows that there is no statistically significant difference between the mutation rate of BRCA1 gene and BRCA2 gene, and the mutation rate of BRCA1/2 is not related to the diagnosis age of the relatives. This study provides a reference for the research of the field, and provides a reference for the future more accurate assessment of breast cancer’s risk in people whose health was at high risk.