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

All cancer types exhibit familial clustering, suggestive of a significant inherited component; however, to date only a few of the genes responsible have been identified and the inherited component, if any, underlying most common cancers has not been well defined. Amongst the important known susceptibility genes are those dominant genes conferring a high risk of breast and ovarian cancer (BRCA1), colon cancer (hMSH2 and hMLH1), and melanoma (MLM). All these genes confer a high lifetime risk of the disease concerned, but are rare and only account for a small minority (less than 5%) of cases. However, there are also commoner genes conferring lower risks but accounting for a more substantial fraction of cancer cases; those so far identified include the ataxia-telangiectasia gene and the HRAS1 minisatellite locus.
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PMID:The inherited component of cancer. 798 39

Studies of familial breast and ovarian cancer have traditionally been directed towards a single type of cancer, but recent evidence leads us to consider these two types of cancer together. The original evidence for a common hereditary basis for breast and ovarian cancer comes from the observation of large families with several cases of both types. The number of cancers in these families was too great to be explained by chance and none of the known environmental risk factors are sufficient to account for the clustering. Statistical analysis performed on a number of breast-ovary cancer families identified by Dr Henry Lynch and his colleagues led them to conclude that the clustering could be explained by the effect of a single dominant gene. Women with breast cancer are at increased risk of developing a second primary cancer of the ovary; and relatives of women with breast or ovarian cancer are at roughly double the risk for either tumour. The most convincing evidence, however, for a common predisposition for breast and ovarian cancer comes from genetic linkage studies. In a linkage study cancer susceptibility in a family is shown to be transmitted with a particular allele of genetic marker of known chromosomal location. A gene from chromosome region 17q12-q21, designated BRCA1, identified in 1990 by Dr Mary-Claire King and colleagues, predisposes to both cancer of the breast and the ovary.
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PMID:Genetics of breast and ovarian cancer. 798 46

BRCA1, a gene predisposing to breast and ovarian cancer, was mapped to chromosome 17q21 by linkage analysis. Loss of heterozygosity in breast and ovarian tumors from BRCA1-linked patients always involved loss of wild-type alleles from chromosome 17q21, suggesting that BRCA1 acts as a tumor suppressor gene. Meiotic recombination in linked families constrained the BRCA1 region to an estimated physical size of 650 kilobases. Twenty-two candidate genes were isolated by screening complementary DNA libraries with yeast artificial chromosomes and cosmids from the critical region. Of these, 8 were known human genes, 7 were homologues of genes identified in other species, and 7 encoded novel transcripts. Each gene were sequenced and analyzed for variation, revealing 44 variants, including two missense mutations in two genes which segregated with breast cancer and were not found in controls. However, no frame-shift, nonsense, or regulatory mutations were found.
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PMID:The search for BRCA1. 798 31

Clinical observations suggest that breast cancer is occasionally inherited as an autosomal dominant disease in families. Epidemiologic studies consistently have shown that a history of breast cancer in a first-degree relative increases a woman's risk of breast cancer when compared with the general population. The risk is similar if a mother or sister is affected and is increased further if both are affected. The difficulty with such an observation is that in itself it does not clarify the nature of the true underlying risk factors which could be genetic or due to the aggregation of environmental risk factors in families. Complex segregation analysis of breast cancer aggregation in families suggests that breast cancer susceptibility is due to an autosomal dominant inheritance of one or more rare genes in a few families in which carriers have a high probability of developing the disease perhaps as great as 100 percent. Close linkage of a breast-cancer-susceptibility gene (BRCA1), between markers of the chromosomal region 17q12-q21 on the long arm of chromosome 17, with breast cancer recently has been reported. Families linked to BRCA1 were more likely to have early onset of breast cancer or have breast and ovarian cancer in the family. It is likely that other genes play a role in the unlinked breast-cancer families. Both the epidemiologic and genetic data suggest that breast cancer is a heterogeneous disease.
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PMID:Familial risk and genetic susceptibility for breast cancer. 799 68

Four genes are now known to be responsible for inherited susceptibility to breast cancer: the BRCA1 gene on chromosome 17q21, the ataxia-telangiectasia (AT) gene (11q22-q23), the TP53 gene (17p13.1) and the androgen receptor (AR) (Xq11.2-q12). These genes, however, differ dramatically in terms of the risk of breast cancer that they confer, the proportion of breast cancer incidence that they account for and the other cancers and other phenotypes with which they are associated. Genetic linkage studies have shown that some high risk breast cancer families, particularly those where breast cancer occurs in association with ovarian cancer, are due to a gene on chromosome 17q known as BRCA1. The BRCA1 gene is estimated to confer a breast cancer risk of about 70% by age 70, and may account for about 2% of overall breast cancer incidence, although a higher proportion of younger cases. Germline mutations in the TP53 gene are responsible for a high proportion of LI-Fraumeni families, in which breast cancer occurs in association with childhood sarcomas and other cancers. In such families, the risk of breast cancer is over 50% by age 50, and the risk of all cancers is nearly 100%; germline TP53 mutations are, however, probably responsible for much less than 1% of all breast cancer. By contrast, heterozygotes for the AT gene carry a much more moderate risk of breast cancer. This gene, however, is much more common in the population and may account for 7% or more of breast cancer incidence. Finally, germline mutations in the androgen receptor are known to cause male breast cancer, but this has only been demonstrated in two families. Evidence from linkage and population based studies suggests that these genes may account for about one half of the observed familial clustering of breast cancer; other breast cancer susceptibility genes therefore remain to be identified.
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PMID:Inherited susceptibility to breast cancer. 801 3

BRCA1, the susceptibility gene for hereditary breast-ovarian cancer, is located on chromosome 17q12-21 but has not yet been identified. Two tandem oestradiol 17 beta hydroxysteroid dehydrogenase genes (17HSD) are assigned to this region. The active 17HSDII gene encodes the normal enzyme which regulates local synthesis of oestrogens, whereas 17HSDI is considered to be a pseudogene. We used reverse transcription coupled to polymerase chain reaction (RT-PCR) and found that the 17HSDI gene was also transcribed in half of the human cell lines and most of the biopsies studied, suggesting that 17HSDI could modulate normal 17HSDII activity in oestrogen target cells. We hypothesize that altered 17HSDI gene expression could lead to both hereditary and/or sporadic breast cancer by increasing local oestrogen concentration and that it is still a potential candidate for BRCA1.
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PMID:17 beta Hydroxysteroid dehydrogenase 1 "pseudogene" is differentially transcribed: still a candidate for the breast-ovarian cancer susceptibility gene (BRCA1). 802 76

Most cancers appear to be sporadic. However, 5 to 10% of cancers occur in genetically predisposed individuals. This inherited genetic risk is observed in syndromes such as familial polyendocrinopathies or phacomatosis such as neurofibromatosis, but also in familial aggregations of frequent cancers such as breast or colon cancers. Thanks to studies on molecular genetics, it has been possible over the last ten years to localize and to identify a large number of predisposing genes. These discoveries have permitted to better understand the biological basis of the predisposition and to offer counselling by identifying at-risk individuals in those families. In the case of multiple endocrine neoplasia type 2 associated with an elevated risk for medullary thyroid cancer, the gene involved is a protooncogene named RET and located on chromosome 10. Point mutations affecting specific regions of this gene are the basis of the genetic predisposition. For familial breast cancer, a susceptibility gene named BRCA1 has been located on the long arm of chromosome 17. Mutation of this gene (yet to be identified) led to very elevated risk of breast cancer and also in some families of ovarian cancer.
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PMID:[Genetic predisposition to cancer: familial forms of medullary thyroid cancer and breast cancer]. 803 90

Family history is recognized widely as a significant risk factor for the development of breast cancer. A gene (BRCA1), mutations in which confer susceptibility to early-onset breast and ovarian cancer, has been mapped to chromosome 17q12-21. An intensive search for this gene is currently underway in a number of laboratories. Recent data support the hypothesis that BRCA1 is a tumor suppressor gene that may be important in the development of both inherited and sporadic breast and ovarian cancers. Genetic and physical maps of the BRCA1 candidate region largely have been completed and efforts are being directed at identification of candidate genes from within this region. A small number of families recently have received results of genetic-linkage testing, indicating which family members likely are to be carriers of a germline BRCA1 mutation, and, therefore, have a lifetime risk of developing breast cancer of approximately 85%. The imminent isolation of BRCA1 will make predictive testing for breast cancer a reality for many women and likely will pave the way for novel diagnostic and therapeutic strategies in the future.
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PMID:Familial breast cancer. Approaching the isolation of a susceptibility gene. 803 34

Breast cancer in men is about a hundredfold less common than in women and this has hindered research into its genetic basis. We have examined 22 families with at least one case of male breast cancer for linkage to the hereditary breast and ovarian cancer locus, BRCA1, on chromosome 17q. We found strong evidence against linkage to BRCA1 (lod score-16.63) and the best estimate of the proportion of linked families was 0% (95% CI 0-18%). Our results indicate that there is a gene(s) other than BRCA1 which predisposes to early-onset breast cancer in women and which confers a higher risk of male breast cancer. Identification of additional pedigrees that include cases of male breast cancer may therefore facilitate the mapping and isolation of this gene.
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PMID:Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. 807 31

A gene (BRCA1) predisposing for familial breast and ovarian cancer has been mapped to chromosome band 17q12-21. Based on the observation that ovarian tumors from families with breast and ovarian cancer lose the wild-type allele in the region for the BRCA1 locus, it has been suggested that the gene functions as a tumor suppressor gene. We have studied chromosomal deletions in the BRCA1 region in seven breast tumors, three ovarian tumors, one bladder cancer, and one colon cancer from patients in six families with breast-ovarian cancer, in order to test the hypothesis of the tumor suppressor mechanism at this locus. We have found a low frequency of loss of heterozygosity at this region, and our results do not support the idea that BRCA1 is a tumor suppressor gene. Alternatively, the disease segregating in these families is linked to one or more different loci.
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PMID:Loss of heterozygosity studies in tumors from families with breast-ovarian cancer syndrome. 807 36


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