| Project/Area Number |
08457437
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
TANAKA Kenichi NIIGATA UNIVERSITY,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,PROFESSOR AND CHAIRMAN, 医学部, 教授 (10126427)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Yoichi NIIGATA UNIVERSITY,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,ASSOCIATED PROFESSOR, 医学部, 講師 (40231774)
TAKAKUWA Koichi NIIGATA UNIVERSITY,DEPARTMENT OF OBSTETRICS AND GYNECOLOGY,ASSOCIATED PROFESSOR, 医学部, 講師 (80187939)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | FAMILIAL OVARIAN CANCER / BRCA1 GENE / LOH / BRCA1遺伝子 / 卵巣がん / 連鎮解析 / BRCA1 |
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| Research Abstract |
We analyzed the alteration of BRCA1 in DNA obtained from 139 individuals of 17 Japanese site-specific ovarian cancer families and 17 breast-ovarian cancer families. Several germline mutations were detected in 18 families, which consisted of 11 breast-ovarian cancer and 7 site-specific ovarian cancer families, by single-strand conformation polymorphism (SSCP) following direct sequence analysis. The mutations included eleven frameshifts, six nonsense mutations, and one missense mutation causing a loss of zinc-binding motif.
The frequency of LOH at the markers on the BRCA1 gene was 57% (8 of 14 cases) in site-specific ovarian cancer families, 100% (6 of 6 cases) in breast-ovarian cancer families. All tumors of the patients carrying mutation of BRCA1 showed deletion of wild-type alleles implicating BRCA1 as a tumor suppresser gene.
In addition, we analyzed clinical features of twenty-three ovarian cancer patients associated with germline mutations of BRCA1 from 5 site-specific ovarian cancer
… More
families and 6 breast-ovarian cancer families in Japan. The average age at diagnosis was 51.3 years old (range, 38 to 77). Histological examination revealed 24 serous cyst-adenocarcinoma in 23 patients. In 19 patients with clear clinical records, one patient had stage I disease, 15 had stage III and 3 had stage IV.With stage III of disease, 13 patients treated with cisplatin-containing chemotherapy following tumor reduction surgery showed higher survival rate, as compared with age and treatment courses matched controls (0.802 vs.0.180, the log-rank test : p<0.05). Disase-free intervals of BRCA1 group was also significantly longer than that of sporadic cases (median disease free survival 59.6 vs. 8.3).These results suggest that the clinical outcome of ovarian cancer with germline mutations of BRCA1 appears to be more favorable as compared with sporadic cases. Finally, our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 50 pedigrees of 12 families. The expected life time risk of ovarian cancer is about 80% for women with mutations of BRCA1 suggesting that the disease penetrance among pedigrees with germline mutations of the BRCA1 gene expressed substantially high level. Less
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