Hereditary ovarian cancer
Family history is the strongest risk factor for ovarian cancer. Three clinical manifestations of hereditary ovarian cancer have been recognized: (1) “site-specific” ovarian cancer, (2) the breast and ovarian cancer syndrome, and (3) the hereditary nonpolyposis colorectal cancer (HNPCC; Lynch II) syn...
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Published in | Human pathology Vol. 36; no. 8; pp. 861 - 870 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Elsevier Inc
01.08.2005
Elsevier Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Family history is the strongest risk factor for ovarian cancer. Three clinical manifestations of hereditary ovarian cancer have been recognized: (1) “site-specific” ovarian cancer, (2) the breast and ovarian cancer syndrome, and (3) the hereditary nonpolyposis colorectal cancer (HNPCC; Lynch II) syndrome. The first 2 groups are associated with germ line mutations in the
BRCA1 and
BRCA2 tumor suppressor genes, whereas HNPCC is associated with germ line mutations in the DNA mismatch repair (MMR) genes, primarily
hMLH1 and
hMSH2. At least 10% of all epithelial ovarian cancers are hereditary, with mutations in the
BRCA genes accounting for approximately 90% of cases and most of the remaining 10% attributable to HNPCC. Hereditary ovarian cancers exhibit distinct clinicopathologic features compared with sporadic cancers. The cumulative lifetime risk of ovarian cancer is 40% to 50% for
BRCA1 mutation carriers and 20% to 30% for
BRCA2 mutation carriers. Both BRCA proteins participate in transcriptional regulation of gene expression as well as the recognition or repair of certain forms of DNA damage, particularly double-strand breaks. Mutations of
BRCA1 and
BRCA2 are mainly of the frameshift or nonsense variety. Most ovarian cancers associated with germ line
BRCA mutations are diagnosed at a younger age and are high-grade and advanced-stage serous carcinomas.
BRCA mutations do not seem to play a significant role in the development of mucinous or borderline ovarian tumors. Hereditary ovarian cancers have a distinctly better clinical outcome with longer overall survival and recurrence-free interval after chemotherapy than sporadic cancers. Women with a family history including 2 or more first- or second-degree relatives with either ovarian cancer alone or both breast and ovarian cancers should undertake prophylactic oophorectomy immediately after childbearing has been completed to reduce the risk of ovarian cancer. The cumulative risk of ovarian cancer in HNPCC families is more than 12%. Ovarian cancer in HNPCC syndrome is diagnosed at younger age than in the general population. Most tumors are low-stage well-differentiated or moderately differentiated carcinomas. Annual follow-up is recommended for these patients. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 0046-8177 1532-8392 |
DOI: | 10.1016/j.humpath.2005.06.006 |