Analysis Of The Characteristics Of BRCA1/2 Mutations And The Clinicopathologic Features Of Familial Breast Cancer In Hebei Province

Objective: Breast cancer is one of the most common malignant tumors which seriously threaten the physical and mental health of women. BRCA1/2 is antioncogene, which participates in the repair of DNA damage, and maintains the integrity of the genome; they are also breast cancer susceptibility gene, closely related to familial breast cancers. We detected the BRCA1/2 gene mutations in Chinese familial and sporadic breast cancer patients to study the differences of BRCA1/2 gene mutations and the clinicopathologic features between familial and sporadic breast cancer.Methods: To study the BRCA1/2 mutations in Chinese familial breast cancer patients, the genomic DNA from peripheral mononuclear blood cells of 111 samples (18 familial breast cancer patients, 50(>35 years old)sporadic breast cancer patients, 23 breast benign tumor patients and 20 health controls) was studied by using Single Strand Conformation Polymorphism Analysis of Polymerase Chain Reaction Products(PCR-SSCP) and DNA sequencing. Clinical data, pathological types, clinical stages, histological grades, the metastatic state of the axillary lymph nodes, estrogen receptor, progestogen receptor and vascular endothelial growth factor of all the the breast cancer patients had been sorted to be analyzed.χ2 and Fisher's exact propability of SPSS 12.0 statistical package was used to do the statistics analysis.α=0.05 was the size of test.Results: 1 681 breast cancer patients accepted operation in the affiliated fourth hospital of Hebei medical university between June 2005 and May 2006, and 18(2.64%) of them were familial breast cancer, which was less than abroad (9.2%) and the recent report in China (4.4% and 5.52%); 2 We have found 5 mutations (162ATT > TTT ; 4142GTT > GTG ;4196CAA > CAT ; 4196delA, 4142GTT > GTG ;5379GAA>AAA) in all the 68 breast cancer samples, which were all sited in BRCA1, the incidence was 7.35% (5/68). All the mutations were the first time to be detected. We didn't found the mutation hot spots of western countries, and no"founder mutations"were found. 3 3 (16.7%) BRCA1 mutations occurred in the familial breast cancer patients, 2 (4.0%) occurred in the sporadic breast cancer patients. The mutation rate of familial breast cancer was much higher than that of sporadic breast cancer, but no significant difference was found (p=0.111). The incidence of BRCA1 mutations in both familial and sporadic breast cancer patients was lower than that of the western countries. The incidence of BRCA1 mutations in familial breast cancer was similar with the recent report in China, but the incidence of BRCA1 mutations in sporadic breast cancer was lower than the recent report in China; 4 A mononucleotide polymorphism site was found, and it was located in the 35th base of the downstream of BRCA1 Exon20 G>A(IVS20+35G>A), which made one arginine was replaced by a histidine. This site hadn't been reported in the related composition or BIC network. It may be a typical mononucleotide polymorphism site of people in Hebei Pronvince; 5 One BRCA2 mutation (TTTCAGA>TGTCAA(6291insG,6294delG) was found in one of the health control, whether she would take breast cancer or not will be further observated; 6 Compared with the non-BRCA1 mutation group, the BRCA1 mutation associated breast cancer has more carcinoma medullare, was poor differentiation and had high grade in tumor cells. ER, PR, CerbB2 and VEGF were less frequently expressed in tumors of BRCA1 carriers than the controls. The results implied Chinese BRCA1 associated breast cancer maybe had similar pathological and immunohisto- chemical features as western patients. But we still need more patients to perform the statistical analysis and confirm the result of our study; 7 Comparing familial breast cancer with sporadic breast cancer patients, the rate of histology III was higher in familial breast cancer, and significant difference was found (p=0.040); No significant difference was found in age, menopause state, tumor size, pathology type, metastasis rate of axillary lymph nodes and clinical stage. ER, PR and CerbB2 in familial breast cancer were less freqently expressed and VEGF was more frequently expressed than that of sporadic breast cancer, but no significant difference was found.Conclusion: 1 The incidence of familial breast cancer in Hebei Province was lower than abroad and that of the other regions of China; 2 5 mutations were found in all the 68 breast cancer samples, which were all sited in BRCA1, and all the mutations were the first time to be detected. We didn't found the mutation hot spots of Western countries, and no"founder mutations"of Chinese were found; 3 The BRCA1 mutations were occurred much in the familial breast cancer patients than in the sporadic breast cancer patients; and BRCA1 mutations in both Chinese familial and sporadic breast cancer were lower than that of western countries. The incidence of BRCA1 mutations in familial breast cancer was similar with the recent report in China, but the incidence of BRCA1 mutations in sporadic breast cancer was lower than the recent report in China; 4 A mononucleotide polymorphism site was found, which was located in the 35th base of the downstream of BRCA1 Exon20 G>A(IVS20+35G>A. It indicated that this site maybe one of the most common mononucleotide polymorphism sites in HeBei province; 5 The BRCA mutations found were concentrated on BRCA1. Compared to the non-BRCA1 mutation group, the BRCA1 mutation associated breast cancer has more carcinoma medullare, was poor differentiation and had high grade in tumor cells. ER, PR, CerbB2 and VEGF were less frequently expressed in tumors of BRCA1 carriers than the controls. The results implied that Chinese BRCA1 associated breast cancer may have similar pathological and immunohistochemical features as western country patients. The clinicopathologic features of BRCA2 associated breast cancer are to be further performed; 6 Comparing the familial to sporadic breast cancer patients, the rate of histology III was higher in familial breast cancer and significant difference was found (p=0.040); But no significant difference was found in age, menopause state, tumor size, pathology type, metastasis of axillary lymph nodes, clinical stage, ER, PR, CerbB2 and VEGF, which indicated that family history wasn't an independent index for breast cancer.