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

Familial clustering of breast cancer has been recognised for over a century but until recently a genetic basis has been suspected rather than proven. Epidemiological studies have tended to support the view that an autosomal dominant gene, with high but incomplete penetrance, accounts for most breast cancer families. However, it is likely that several different predisposing genes are present within most populations. Difficulties arise in a conventional 'linkage mapping' approach to identifying these genes, first, because it is not clear that genetically homogeneous groups of families can be recognised on the basis, for example, of mean age of onset or pattern of other cancers within the kindred and, second, because breast cancer is so common (affecting almost one in twelve women) that large affected kindreds are likely to include an admixture of sporadic (non-genetic) cases. Cytogenetic and 'Loss of Heterozygosity' (LOH) studies in sporadic breast cancers have pointed to several candidate loci for breast cancer genes but there is no clear consensus from these two approaches that might direct attention to any prime target region. Recent reports of tight linkage between familial breast cancer (early onset) and breast/ovarian cancer (regardless of mean age of onset) and a locus on chromosome 17q21 defined by the anonymous probe CMM86, have not been confirmed in detail but have led to the identification of a locus some 15 Mb centromeric of CMM86 that gives a high positive lod at very low recombination fraction in fifteen Edinburgh breast and breast/ovarian cancer families. The disease in the majority of such families therefore appears to be attributable to a mutant gene at 17q12-21. A much smaller proportion of familial breast cancer is accounted for by mutations in the p53 gene (17p13). Not all such families fulfil the criteria for Li-Fraumeni syndrome and not all of the inherited mutations lie within exon 7 of p53. Counselling of members of breast cancer families becomes more exacting as these genetic lesions are identified. It is essential to extend the collection of data and tissue (blood or fixed pathology material) as widely as possible to confirm linkage to a specific locus within each individual kindred, to define the precise mutation and to establish the cancer phenotype and its penetrance. In the course of these studies a substantial population of women at high risk of breast (and other) cancer will be identified. Resources should be directed to this population so that optimum procedures for screening and prevention can be developed.
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PMID:Familial breast cancer. 151 Nov 56

Hereditary breast cancer is common and accounts for approximately 10-14% of all breast cancers. Knowledge of a family history of breast cancer may significantly influence diagnosis and therapy. Genetic heterogeneity has been demonstrated in familial breast cancer. Recently inherited mutations in the tumor suppressor gene p53, have been shown to be the underlying defect in the Li-Fraumeni syndrome. We have shown that defects in this gene also play a role in the predisposition to other familial breast cancers. The gene responsible for early onset familial breast and ovary cancer has recently been mapped to chromosome 17q21. For most of the sporadic breast cancers a multifactorial model, including variable genetic and environmental factors, has been considered. Two genetic risk factors which may predispose for a considerable portion of breast cancers are the gene causing ataxia telangiectasia (AT) and the gene that gives rise to proliferative breast disease (PBD). Identification of distinct genes enhancing the risk of breast cancer will give us the opportunity to identify high risk individuals. Such individuals may benefit from periodic examination affording the possibility of early diagnosis and treatment.
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PMID:Role of genetic factors in breast cancer susceptibility. 162 29

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

Since the discovery of the retinoblastoma tumor suppressor gene many others have been described associated with a variety of different familial syndromes. These include the Li-Fraumeni syndrome, familial breast/ovarian cancer, multiple endocrine neoplasia (MEN1), neurofibromatosis 1 and 2, tuberous sclerosis and von Hippel-Lindau disease. Persons harboring a germ line mutation in a tumor suppressor gene are not born with disease, merely the predisposition to develop one. This is due to the fact that they have inherited only one functional copy compared to persons with no predisposition who have two copies. Germ line mutations have not to be inherited, they can result from a spontaneous mutation occurring during gametogenesis in one patient. Persons with an inherited or de-novo germ line mutation have similar risks to develop multiple cancer or to transmit the defective gene to their offspring. The genes can be analyzed by molecular genetic techniques allowing for a precise genetic diagnosis as well as reliable genetic counselling.
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PMID:[Tumor suppressor gen mutation in the germ line: its significance in familial and sporadic tumors]. 767 34

The isolation of genes that predispose to familial disease is an important goal in cancer research. The identification of such genes "opens up" the possibility of genetic diagnosis in families so that individuals who are at risk of cancer through inheriting a predisposing mutation can be identified. Genes that are involved in familial cancer syndromes may also be important in the pathogenesis of sporadic forms of the disease, which are often more common. In the search for genes that predispose to familial breast and ovarian cancer much recent progress has been made. A locus on the long arm of chromosome 17, in the interval 17q12-21, has been identified by genetic linkage, and appears to be responsible for disease in approximately 40% of breast cancer families and most families that contain breast and ovarian cancer. The region containing this locus, which has been called BRCA1, has been narrowed to a 3-4 cM interval defined by THRA1, the thyroid hormone receptor locus alpha, and D17S183, an anonymous microsatellite polymorphism. Loci other than BRCA1 that have been identified appear not only to predispose to breast and/or ovarian tumors, but to tumors at other sites too. A new locus has been identified on chromosome 2 which is linked to hereditary non-polyposis colorectal cancer (HNPCC). Families with HNPCC are also at risk of endometrial cancer and tumors of the ovary, amongst other cancer sites. Finally, mutations in the p53 gene are inherited in families with Li-Fraumeni syndrome, a rare cancer syndrome predisposing to breast tumors, sarcomas, leukemia and other cancers. Li-Fraumeni syndrome is also the only inherited cancer syndrome that predisposes at least in part to breast cancer where the actual predisposing gene is known. For the other cancer syndromes, the cloning of the predisposing genes is eagerly awaited.
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PMID:Predisposing genes in breast and ovarian cancer: an overview. 811 68

Thirty-seven ovarian cancer-prone families have been identified through a French co-operative network. Three main clinical presentations were observed: site-specific ovarian cancer, breast/ovarian carcinoma syndrome and Lynch syndrome II. An additional kindred with features of Li-Fraumeni syndrome is reported. It is expected that a better understanding of the mechanisms of carcinogenesis will allow the development of new methods of screening and treatment. With this aim, recent studies have mapped the gene for early-onset familial breast cancer and breast/ovarian carcinoma syndrome to the same locus in the chromosome 17q12-q23 region. Results from linkage analysis of two breast/ovarian carcinoma families and three breast cancer families favour the hypothesis of genetic heterogeneity among breast and ovarian tumors.
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PMID:Familial ovarian carcinoma: pedigree studies and preliminary results from linkage analysis. 817 63

Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.
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PMID:Genetic heterogeneity in breast cancer susceptibility. 869 52

Germline mutations in the p53 tumor suppressor gene are associated with the Li-Fraumeni syndrome, characterized by childhood sarcoma, leukemia and early onset breast cancer and has occasionally been found also in familial breast-ovarian cancer. Most mutations found are of missense type and located in the central region of the gene (exons 5 to 8). In the present study, a germline p53 alteration was identified in a late onset breast cancer family (kindred Lund 5; mean age 58 years) using single stranded conformation polymorphism and sequence analysis. The mutation (a CCG to CTG transition) at codon 82 in exon 4, resulting in a proline to leucine substitution, has not previously been reported and was not present in a control set of 60 healthy individuals. Three of five woman with breast cancer (45, 57 and 65 years) were carriers of the alteration. Loss of heterozygosity at the p53 locus was not seen in the primary tumors of these women, but appeared as a partial loss of the wildtype allele in subsequent recurrent lesions of two gene carriers. The family manifested no linkage to the p53 gene (a two-point LOD-score of -0.41), and has previously also been excluded for linkage to the BRCA1 and BRCA2 loci, as well as being carrier of a BRCA1 germline mutation. Although it seems unlikely that the p53 germline mutation is the major cause of disease predisposition in Lund 5, the data suggest that some p53 alteration may confer a subtle influence on breast cancer development and progression.
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PMID:A novel p53 germline alteration identified in a late onset breast cancer kindred. 871 Mar 80

Identification of inherited cancer-predisposing genes offers opportunities for cancer prevention. Inherited susceptibility genes have been identified, primarily through studies of unusual cancer cases and families but also through general population studies. Examples include the RB1 gene for retinoblastoma; the WT1 gene for Wilms' tumor; germline p53 mutations in families with the Li-Fraumeni syndrome; the NF1 and NF2 genes for neuroblastomatosis, types 1 and 2; the VHL gene for renal cancer and other tumors associated with Von Hippel-Lindau disease; the APC gene for adenomatous polyposis coli; the BRCA1 gene for hereditary breast and ovarian cancer; and the mismatch repair genes for colon and other common cancers. For some cancers, identification of gene carriers might be beneficial for targeting screening and chemopreventive interventions. On the other hand, predisposition testing for cancer has the potential for harm from loss of insurability and employability, psychological distress, social stigmatization and other adverse effects. Research is needed to identify predisposition testing procedures that maximize benefits while minimizing harm to subjects. Chemoprevention trials in genetically susceptible populations offer the prospect of finding effective methods of reducing future cancer risk.
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PMID:Identification and management of inherited cancer susceptibility. 874 2

Breast cancer is the most common form of cancer in women in the U.S. The risk factors for developing breast cancer include increasing age, a family history of breast cancer, and the lack of a child by age 30. A substantial fraction of breast cancer, however, occurs in women who have no identifiable risk factors. The diagnosis, pathology, treatment, and presymptomatic testing of cancer susceptibility genes are reviewed. Syndromes with an associated risk of breast cancer are described, such as hereditary breast-ovarian cancer syndrome, Li-Fraumeni syndrome, ataxia telangiectasia, and Cowden's disease. With the localization of the BRCA1 gene to chromosome 17q21 and the BRCA2 gene to chromosome 13q12, issues surrounding breast cancer susceptibility genetic testing are assuming an ever greater measure of importance. The sensitivity and specificity for molecular testing of cancer susceptibility genes, however, have not been well defined. The progress in presymptomatic genetic testing is further hampered by various factors such as the technical difficulty in distinguishing mutations from polymorphisms, the number of different mutations identified thus far and the possibility of false positive and false negative results. Laboratory quality assurance/quality control issues are of paramount importance to avoid misleading interpretations. Many issues surrounding genetic screening and testing, such as insurance and employment discrimination, privacy, and informed consent, are under active debate, and guidelines and standards are under active development. It is therefore important to proceed with caution, so that irreversible harm resulting from data misinterpretation can be avoided.
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PMID:Clinical and research issues in breast cancer genetics. 887 57


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