| Objectives: Breast cancer is one of the most common malignant tumor,and its incidence in the world is a obviously upward trend, which seriouslyendangers the physical and mental health of the majority of women. Thepathogenesis of breast cancer is unclear. Many studies tend to thedevelopment of mammary epithelial cells in a variety of carcinogenic factors,which leads to the gene mutations and the abnormal proliferation. Studiesfound that about5%-10%of cases with familial aggregation and genetictendency in patients with breast cancer. Presently, BRCA1and BRCA2genesare in more clinical applications, and generally well received by domestic andforeign experts and scholars' attention. In this study, it focuses on thecircumstances and characteristics of the Hebei Province of familial breastcancer patients and their healthy female relatives of BRCA1and BRCA2genemutations. And its result contributes to early detection and prevention ofbreast cancer, and provides new ideas for the future of breast cancer genediagnosis and gene therapy.Methods: Select64cases from the Hebei Province of different pedigreesof familial breast cancer.patients and the conditions of the34healthy femalerelatives of information in their lineage. Genomic DNA is collected from theperipheral blood mononuclear cells, and the coding sequences and exon-intronboundaries of BRCA1genes are screened byusing denaturing highperformance liquid chromatography (DHPLC). Then the abnormal fragmentswere confirmed with direct DNA sequencing.Results:1The morbidity of familial breast cancerThere are3335cases breast cancer patients in the Fourth Hospital ofHebei Medical University Breast Center from January2008to April2011. In of all,64cases familial breast cancer patients are accounting for1.91%of alldbreast cancer at the same period. Less than9.2%of the westen countries, andalso lower than other parts of our country (3.3%and4.8%).2In64cases familial breast cancer patients, we found that the fivedisease-related BRCA1mutations, which are all located in exon11of theamplified region. BRCA1gene mutation rate in the familial breast cancerpatients is7.81%, which according with other parts of our country, alsoslightly lower than the population of the westen countries and other parts ofAsia. But it did not find the gene mutation on the BRCA2gene.3In64cases familial breast cancer patients, we found five patients withBRCA1gene mutation. There are2543T>A nonsense mutation,3180delGGframeshift mutation,3413delA frameshift mutation, and2229delAA frameshift mutation. At the same time, we found one single nucleotidepolymorphisms on BRCA1gene, which is2413delA> G; and three ones onBRCA2gene, which are4035delC> T,3199delA> G and3624delC> T.4The clinical and pathological features of BRCA1gene mutations inbreast cancer patients: Familial breast cancer in BRCA1mutation group hadmore menopause patients (60.0%) than non-mutation group (32.2%); mutanttumor size of2~5cm (60.0%) in mutation group is higher than thenon-mutation group (16.9%); the pathological type of mutation group are allinvasive ductal carcinoma; clinical stage â…¡ (60.0%) in mutation group morethan non-mutation group (33.9%); in mutation group, histological grade â…¢(20.0%) more than non-mutation group (6.8%); tumor immunohistochemicalcharacteristics: mutation group of ER-negative (20.0%) higher thannon-mutation group (37.3%); in mutation group PR-negative (40%) andnon-mutation group (37.3%); the mutations group HER-2negative (100.0%)and non-mutation group (74.6%).5From the same family lineage, two breast cancer patients found nocorrelation of BRCA1and BRCA2gene mutations.6Exon11of the BRCA1gene is being2543T> C missense mutation,resulting in No.847amino acid serine (Ser) into a final code. The site is in the primary breast cancer patient and her healthy female relative, who come fromthe same family.Conclusions:1The morbidity of familial breast cancer in Hebei province is lower thanwesten country and domestic other areas.2BRCA1gene mutation rate of familial breast cancer in Hebei provinceis lower than the foreign region, and is similar to the other areas of ourcountry.3BRCA1gene mutations in familial breast cancer patients are all occurred in exon11, two mutations are the first discovered, which were not reportedin the literature of Western countries mutation hot spots. And there is no theancestor mutation of the Chinese population in this study.4One single nucleotide polymorphisms was found in the BRCA1gene,which is2413delA>G in the exon11. This site maybe is a commonpolymorphism in the population of Hebei province.5The five breast cancer-related mutations are all on the BRCA1gene.BRCA1mutations of familial breast cancer in Hebei region has a highproportion of breast invasive ductal carcinoma, histological gradeâ… ~â…¡ gradehigh proportion, and the negative rate of ER, PR, and HER2increased.BRCA2mutations related to breast cancer clinical and pathological is to befurther studied.6From the same family lineage of breast cancer patients has not revealedthe existence of mutations in the BRCA genes. It is one of the factors thatfamilial breast cancer in Hebei region population in low heritability, which isthe BRCA gene mutation rate, is relatively low.7Exon11of the BRCA1gene is being2543T> C missense mutation,which is from the breast cancer patient and her healthy female relative in thesame family. It suggests that the specific lineage mutation, and also may bespecific to familial breast cancer patients in Hebei. |
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