| Epidemic research show that apart from the environment factors, the hereditary factors play an important role in the carcinogenesis and development of ovarian and breast cancer. About 3%-7% ovarian and breast cancer has familial history. BRCA genes (including BRCAl and BRCA2) are hereditary breast cancer and hereditary ovarian cancer susceptible genes. BRCA genes are tumor suppressor genes. This two genes can explain 30% hereditary ovarian cancers and 40%-50% hereditary breast cancers. BRCA genes take part in the harmed DNA mending process, maintain gene integrity and make the cell in which DNA has been damaged apoptosis, inhibit the pathogenesis and development of tumors. Mutations of BRCA genes may conduct the BRCA proteins to truncate and these truncate proteins lose the ability of mending damaged DNA. The damaged DNA can't be repaired and the accelerating harms induce carcinogenesis. There are more than onehundred types of BRCA gene mutations. Most of these mutations are shift mutation, nonsense mutation, cut site mutation and so on. Detecting BRCA2 gene mutation has important clinical significance. Let the women who have cancer familial history do regular gene test in order to find BRCA mutation gene carriers, enhance genetic counseling, checking and prophylactic methods in order to diagnosis and treat patients in early stage to reduce cancer onset and death rate. This research use PCR-SSCP-DNA stained method to test the BRCA2 6174del T mutation (in 11 exon 2003 code delete one base T) in the samples collected.Materials and Methods 58 ovarian cancer and breast cancer paraffin-embedded tissue block specimens were obtained from Zhengzhou University Medical Collage Pathology Department from 1995 to 2000. 42 sporadic ovarian cancer tissue blocks were picked up. The patients' ages ranged from 25 to 82 years old, the mean age was 57.8 + 8.73. Among these sporadic ovarian cancers there were 25 ovarian serous cystadenocarcinoma, 8 ovarian mucinous cystadenocarcinoma, 6 ovarian endometrioid carcinoma, 3 other type. Of FIGO stage: there were 7 19 14 2 cases, in stage I II III IV respectively. In 12 familiar ovarian cancers ,The patients' ages ranged from 27 to 64 years old, the mean age was 49.58 + 10.11. There were 11 ovarian serous cystadenocarcinoma, 1 ovarian mucinous cystadenocarcinoma. Of FIGO stage: there were 1 6 4 1 cases, in stage I II III IV respectively. All the 4 familial breastcancers were breast invasive ductal carcinoma.10 11 m 5 sections were sliced continuously from every paraffin-embedded tissue blocks. The sections were deparaffinized and extracted genome DNA. The PCR primer sequence were extracted from article detecting mutation of BRCA2 6174 del T. PCR products were tested by 2% agarose gels electrophoresis. 10 u 1 formamide denaturant were added to 10 u. 1 PCR products and mixed. The mixture were incubated in 98?C water for 10 minutes then placed in 0?C ice water at once. The double-stranded DNA denatured into single-stranded DNA and maintained this condition. These denatured samples were showed by silver-staining polyacrylamide gel using steady voltage lasting 24 hours. The results were taken photos and analysed.Results1. The mean age at diagnosis of 12 familial and 42 sporadic ovarian cancers were 49.58+10.11 and 57.8 + 8.73 years old, respectively. Familial ovarian cancer occured earlier than sporadic one. (P=0.007).2. In 12 familial ovarian cancers, there were 11 ovarian serous cystadenocarcinoma (91.66%). However, in 42 sporadic ovarian cancers there were 25 ovarian serous cystadinocarcinoma (59.5%). The difference was significant. (P=0.021).3. Stage at diagnosis had no difference between familial and sporadic ovarian cancer.4. In 12 familial ovarian cancers, 2 had been observed mutation (16.67%). No mutation was found in 42 sporadic ovarian cancers. (P=0.046).Conclusions1. The most common BRCA2 mutation in foreign people was BRCA2 6174del T. This mutation was less in Chinese(16.67%) than that in foreigners(30%).2. Sporadic...
|
PDF Full Text Request