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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of genes are known to be involved in inherited susceptibility to breast and/or ovarian cancer. In the context of high-risk families the most important genes are BRCA1 on chromosome 17q, which is associated with a high penetrance of both breast and ovarian cancer, and BRCA2 on chromosome 13q, which causes a high risk of breast cancer but a lower risk of ovarian cancer. Other high-risk cancer genes that confer increased risks of breast or ovarian cancer in addition to other cancers include the hereditary non-polyposis colorectal cancer genes and the TP53 gene, which causes breast cancer as part of the Li-Fraumeni syndrome. The predisposing mutations in these genes are relatively rare in the population. More common genes which are associated with an increased, but lower, risk of breast cancer are the ataxiatelangiectasia gene and the HRAS1 gene. This paper reviews recent progress in mapping and cloning of these susceptibility genes, and provides estimates of the cancer risks associated with each gene and the frequency of predisposing mutations.
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PMID:The genetics of breast and ovarian cancer. 754 24

There is now unequivocal evidence that an estimated 5% of breast cancer cases is inherited in families. Inherited predisposition of cancer in these families is thought to be the result of a mutation in one of several highly penetrant autosomal dominant genes such as BRCA1 or BRCA2. The BRCA1 gene which is localized on chromosome 17 q was recently isolated and at about the same time BRCA2 was localized to chromosome 13 q. A number of other genetic mutations is also associated with predisposition to breast cancer but accounts for a very small proportion of inherited breast cancer. Many women want to know whether they have inherited a gene predisposing to breast cancer. Those with a family history of breast cancer are particularly concerned about their risk of disease. Currently the assessment of an individual's risk of breast cancer can be undertaken using prediction models based on family history and can be further refined when molecular genetic investigations became available. Without molecular characterisation the Claus tables derived from the Cancer and Steroid Hormone Study data set are best suited to predict breast cancer risk based on age of onset of affected relatives. Direct screening for mutations in breast cancer genes in not yet generally available. Testing for inherited susceptibility is currently being offered to selected families where multiple cases of breast and/or ovarian cancer are diagnosed at an early age (younger than 45 years) as part of research protocols. In these families the so-called indirect gene analysis for linkage of disease to BRCA1 and BRCA2 or the direct analysis of mutations with functional significance in the BRCA1 gene allows relatively refined risk assessment for non-diseased female family members. Some examples will be presented to illustrate risk assessment in different familial and individual situations. Risk assessment including test result interpretation and counselling can be appropriately provided directly to the patient by physicians and genetic counsellors in a coordinated genetic counselling setting.
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PMID:[Risk assessment for familial occurrence of breast cancer]. 757 5

The recent cloning of a breast-ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility. This study examined interest in and expectations about an impending genetic test among first-degree relatives (FDRs) of breast cancer patients. One hundred five females completed two structured telephone interviews to assess demographics, breast cancer risk factors, psychological factors, and attitudes about genetic testing for breast cancer susceptibility. Overall, 91% of FDRs said that they would want to be tested, 4% said they would not, and 5% were uncertain. The most commonly cited reasons for wanting genetic testing were to learn about one's children's risk, to increase use of cancer screening tests, and to take better care of oneself. Women with less formal education were motivated by childbearing decisions and future planning to a greater degree than were women with education beyond high school. Most women anticipated a negative psychological impact of positive test results, involving increased anxiety (83%), depression (80%), and impaired quality of life (46%). In addition, 72% of women indicated that they would still worry if they tested negative. In multivariate regression analysis, level of baseline depression was the strongest predictor of an anticipated negative impact of genetic testing (Beta = .15; P, .0001). These results suggest that the demand for genetic testing for breast cancer susceptibility may be great, even among women who are not likely to have predisposing mutations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interest in genetic testing among first-degree relatives of breast cancer patients. 767 39

The breast cancer susceptibility gene BRCA1 has been cloned and a second susceptibility gene, BRCA2, chromosomally mapped; will most breast and ovarian cancer turn out to be familial?
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PMID:Familial breast cancer. BRCA1 down, BRCA2 to go. 787 85

A small proportion of breast cancer, in particular those cases arising at a young age, is due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. A genomic linkage search was performed with 15 high-risk breast cancer families that were unlinked to the BRCA1 locus on chromosome 17q21. This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13. Preliminary evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer.
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PMID:Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. 809 Dec 31

Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning approximately 850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred independently in two families. In one family, penetrance was complete, with females developing early-onset breast cancer or ovarian cancer and the male carrier developing prostatic cancer, whereas, in the other family, penetrance was incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two novel nonsense mutations led to the loss of mutant BRCA1 transcript in families with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt segment of the BRCA1 3'-UTR and 1.3 kb of genomic sequence including the putative promoter region were invariant by single-strand conformation analysis in 13 families without coding-sequence mutations. Overall in our series, BRCA1 mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7 with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not tested for linkage. Three other families have positive lod scores for linkage to BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores for both BRCA1 and BRCA2.
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PMID:Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families. 853 57

An estimated 5 to 10% of all breast and ovarian cancer is attributable to inherited mutations in two highly penetrant autosomal dominant susceptibility genes, BRCA1 and BRCA2. BRCA1 confers higher risk of ovarian cancer and BRCA2 much higher risk of male breast cancer. With the exception of missense mutations in the RING finger near the amino terminus of BRCA1, virtually all germline mutations in the gene cause the novel BRCA1 protein to be prematurely truncated. Approximately 90% of breast tumors in BRCA1 families, 50% of unselected breast tumors and 65-80% of unselected ovarian tumors have lost one allele of BRCA1 by somatic deletion. Very few tumors have detectable somatic point mutations in BRCA1. Inhibition of BRCA1 expression in mammary epithelial cell lines also suggests that BRCA1 may act as a tumor suppressor. The biological function of BRCA1 is still unknown, although identification of a patient homozygous for an inherited BRCA1 mutation suggests that the gene's function may be essential only to specific tissues. At least two other genes, P53 and the androgen receptor, are responsible for inherited predisposition to breast cancer in rare families. Several epidemiologic studies suggest that individuals carrying rare alleles at a minisatellite flanking the HRAS locus are at increased risk of cancer, including breast cancer. Finally, preliminary epidemiologic studies also suggest that individuals heterozygous for mutations in the ataxia telangiectasia gene may be at increased risk of breast cancer.
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PMID:Inherited breast and ovarian cancer. 854 81

Studies of the etiology, early detection, and prevention of breast cancer reported in the past year are reviewed in this paper. Studies of the etiology of breast cancer include reports on genetic and environmental factors. A major advance in the study of inherited forms of breast and ovarian cancer occurred with the identification of the BRCA1 gene. A second breast cancer susceptibility gene, the BRCA2 gene, was localized to chromosome 13q12-13. Multiple mutations in the BRCA1 gene have been identified, presenting a challenge for the development of predictive testing. Controversy continues over the association between hormone replacement therapy and the development of breast cancer. A study of exercise suggests a strong protective effect against the development of early onset breast cancer. Recent studies have failed to find a strong link between dietary fat intake and the development of breast cancer. A meta-analysis of studies of the efficacy of screening for the prevention of breast cancer mortality demonstrates a significant reduction in mortality among women 50 years of age and older. A lowering of breast cancer mortality for women aged 40 to 49 was only demonstrated after 10 to 12 years of follow-up. The risks and benefits of tamoxifen therapy, a potential breast cancer chemoprevention agent, continue to be clarified. Adverse effects on the endometrium, including an increased risk of endometrial cancer, have been reported. Beneficial effects include an improved cardiovascular risk profile and preservation of bone mineral density among postmenopausal women.
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PMID:Epidemiology, prevention, and early detection of breast cancer. 854 94

Recent advances in our understanding of the genetic characteristics of cancer will change approaches to genetic screening and counselling. Cancer results from multiple, cumulative mutations in genes that regulate cell replication and differentiation. In familial cancer a germ-line mutation is passed on in an autosomal dominant pattern, but cancer will develop in people who inherit the defect only if other mutations also occur in susceptible somatic cells. The tumour-suppressor gene known as BRCA1 is thought to affect half of those families who have an inherited breast cancer syndrome and most families with a breast and ovarian cancer syndrome. Another gene, BRCA2, is thought to affect most of the remaining families with a breast-cancer-only syndrome. Hereditary nonpolyposis colon cancer (HNPCC) is caused by mutations in surveillance genes that protect DNA from the spontaneous errors that occur during cell division. Because there are no outcome data on which to base practice guidelines for genetic screening or management of asymptomatic carriers in families at risk, testing should be restricted to research settings.
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PMID:Genetic counselling and testing for susceptibility to breast, ovarian and colon cancer: where are we today? 854 3

Germline mutations in BRCA1 are responsible for most cases of inherited breast and ovarian cancer. However, the function of the BRCA1 protein has remained elusive. We now show that BRCA1 encodes a 190-kD protein with sequence homology and biochemical analogy to the granin protein family. Interestingly, BRCA2 also includes a motif similar to the granin consensus at the C terminus of the protein. Both BRCA1 and the granins localize to secretory vesicles, are secreted by a regulated pathway, are post-translationally glycosylated and are responsive to hormones. As a regulated secretory protein, BRCA1 appears to function by a mechanism not previously described for tumour suppressor gene products.
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PMID:BRCA1 is secreted and exhibits properties of a granin. 867 23


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