Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 5-10% of breast and ovarian cancer cases are due to an inherited susceptibility. The majority of inherited breast and ovarian cancer susceptibility is due to mutations in the BRCA1 and BRCA2 genes; however, other genes responsible for inherited susceptibility to these diseases are yet to be identified. A small proportion of inherited breast and ovarian cancers are due to other genetic cancer susceptibility syndromes including Li-Fraumeni syndrome, Cowden disease and hereditary non-polyposis colorectal cancer. It is recommended that individuals at risk for inherited susceptibility to breast and/or ovarian cancer who are requesting DNA testing be provided with pre-test genetic counseling and education and post-test counseling and follow-up to ensure that all aspects of genetic testing have been disclosed and that the patient has truly given informed consent.
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PMID:Inherited susceptibility to breast and ovarian cancer. 948 22

Host-cell reactivation (HCR) of UV-C-irradiated herpes simplex virus type 1 (HSV-1) has been determined in skin fibroblasts from the following hereditary cancer-prone syndromes: aniridia (AN), dysplastic nevus syndrome (DNS), Von Hippel-Lindau syndrome (VHL), Li-Fraumeni syndrome (LFS) and a family with high incidence of breast and ovarian cancer. Cells from AN, DNS or VHL patients were found to exhibit heterogeneity in HCR. Cells from individuals belonging to an LFS family show reduced HCR in all cases where the cells were derived from persons carrying one mutated p53 allele, whereas cells derived from members with two wild-type alleles show normal HCR. LFS cells with reduced HCR also reveal reduced genome overall repair, and a slower gene-specific repair of the active adenosine deaminase (ADA) gene, but little if any repair of the inactive 754 gene. In the breast/ovarian cancer family, reduced HCR is observed in skin fibroblasts derived from both afflicted and unaffected individuals. In addition, these cells display lower survival after exposure to UV-C and exhibit higher levels of SCEs than those in normal cells. These observations indicate that various hereditary cancer-prone syndromes, carrying mutations in different tumor-suppressor genes, exhibit an unexplained impairment of the capacity to repair UV-damaged DNA.
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PMID:Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer-prone syndromes. 963 47

Mutations in BRCA1 and BRCA2 account for a large portion of the inherited predisposition to breast and ovarian cancer. It was recently discovered that mutations in these two genes are less common in the Finnish population than expected. Because the genetic background of breast cancer, in particular, is largely obscure, it became necessary to search for mutations in other susceptibility genes. Because seven of our BRCA1 and BRCA2 mutation-negative families fulfilled the criteria of either Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL), we decided to screen them for germ-line TP53 mutations in exons 5-8 using a dual-temperature single-strand conformation polymorphism assay (SSCP). Two missense mutations (Asn235Ser and Tyr220Cys) were identified. The clinical significance of these findings was evaluated by comparison to previously reported germ-line TP53 mutation data, and by using the tumor loss of heterozygosity (LOH) analysis. In addition, an immunohistochemical analysis of tumor specimens from mutation-positive individuals was performed. Our results suggest that the observed missense mutations confer susceptibility to cancer, and that germ-line TP53 mutations would therefore explain an additional fraction of hereditary breast cancer in Finland.
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PMID:Germ-line TP53 mutations in Finnish cancer families exhibiting features of the Li-Fraumeni syndrome and negative for BRCA1 and BRCA2. 1043 28

The medical histories of breast cancer-prone families have been described for over a century. The pattern of breast cancer occurrences in these families is most consistent with an autosomal dominant mode of inheritance. The location of a gene that could explain the pattern of transmission of the breast cancer trait in families averaging early (pre-menopausal) onset of breast cancer was reported in 1990. Since then, two genes have been identified: BRCA1 and BRCA2. Germ-line mutations in these two genes confer susceptibility to breast (female and male) and ovarian cancer, and account for a significant proportion of hereditary breast cancer in two cancer syndromes: site-specific breast cancer and the breast-ovarian cancer syndrome. Other hereditary syndromes that feature breast cancer are Li-Fraumeni syndrome, Cowden disease, and ataxia telangiectasia, whose carriers have been shown to harbor germ-line mutations in TP53, PTEN, and ATM, respectively. There may be other genetic factors that contribute to hereditary breast cancer, since not all families with multiple cases of breast cancer harbor germ-line BRCA1 or BRCA2 mutations. Host factors (such as lifestyle choices) and other genes may modulate risk of breast cancer in mutation carriers.
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PMID:Genes implicated in hereditary breast cancer syndromes. 1080 49

The nationwide Swedish Family-Cancer Database was used to analyse the risk of cancer among the offspring of bilateral breast cancer patients. We studied 4,734 such mothers who had 9,391 offspring, of whom 328 presented with a primary cancer in the years 1958-1996. Standardised incidence ratios (SIRs) were increased for breast [SIR 3.05, 95% confidence interval (CI) 2.57-3.59], ovarian (SIR 1.84, 95% CI 1.03-3.05) and anogenital (SIR 1.75, 95% CI 1.11-2.63) cancers and childhood sarcomas (SIR 9.39, 95% CI 1.93-29.13). Additionally, squamous-cell skin cancer was increased among sons and all childhood cancers among daughters. When analysed by histological type, adenocarcinomas of the breast and ovary, all squamous-cell carcinomas and tumours at glandular epithelium (seminomas and intestinal carcinoids) were increased. Mothers with bilateral breast cancer had an excess of 2 or more children with cancer. The increased risk of ovarian cancer is consistent with germline mutations in the BRCA1 and BRCA2 genes, while the risk of soft tissue and bone sarcomas may reflect the association of these tumours with Li-Fraumeni syndrome. The increases in squamous-cell carcinomas at many sites may reflect a new susceptibility syndrome.
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PMID:Familial cancer risks to offspring from mothers with 2 primary breast cancers: leads to cancer syndromes. 1096 44

Germ-line mutations in BRCA1 and BRCA2 genes result in a significantly increased risk of breast and ovarian cancer. Other genes involved in an increased predisposition to breast cancer include the TP53 gene, mutated in Li-Fraumeni syndrome. To estimate the frequency of germ-line mutations in these three genes in Upper Silesia, we have analyzed 47 breast/ovarian cancer families from that region. We found five different disease predisposing mutations in 17 (36%) families. Twelve families (25.5%) carried known BRCA1 mutations (5382insC and C61G), four families (8.5%) carried novel BRCA2 mutations (9631delC and 6886delGAAAA), and one family (2%) harbored novel mutation 1095del8 in the TP53 gene, which is the largest germline deletion in coding sequence of this gene identified thus far. The 5382insC mutation in BRCA1 was found in 11 families and the 9631delC mutation in BRCA2 occurred in three families. These two mutations taken together contribute to 82% of all mutations found in this study, and 30% of the families investigated harbor one of these mutations. The very high frequency of common mutations observed in these families can only be compared to that reported for Ashkenazi Jewish, Icelandic, and Russian high-risk families. This frequency, however, may not be representative for the entire Polish population. The observed distribution of mutations will favor routine pre-screening of predisposed families using a simple and cost-effective test.
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PMID:High frequency of recurrent mutations in BRCA1 and BRCA2 genes in Polish families with breast and ovarian cancer. 1110 77

This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family history that includes at least three generation pedigrees, an appropriate cancer risk assessment and an effective genetic counseling). At present, the most useful methods of risk assessment are those performed on the following genes: BRCA1 and BRCA2 especially for hereditary breast and ovarian cancer, hMLH1 and hMSH2 for hereditary non polyposis colorectal cancer, APC for familial adenomatous polyposis, ret for medullary thyroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and RB1 for retinoblastoma. In conclusion, the development of new diagnostic tests will permit a more accurate assessment of risk in individuals who have not so far shown any sign or symptom of the disease.
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PMID:Hereditary common cancers: molecular and clinical genetics. 1120 30

Cancer risk programs rely on accurately reported family history information. This study compares the accuracy with which cancer sites and ages at diagnosis are reported by Li-Fraumeni syndrome (LFS) and hereditary breast-ovarian cancer syndrome (HBOCS) families undergoing genetic testing. We analyzed the accuracy of 191 cancer diagnoses among first-degree (FDRs) and second-degree (SDRs) relatives reported by 32 LFS and 52 HBOCS participants in genetic testing programs. Cancer diagnoses of relatives were more accurately reported in the HBOCS cohort (78%) than in the LFS cohort (52%). Almost all breast cancer diagnoses were accurately reported, whereas 74% of ovarian cancer diagnoses and only 55% of other LFS-related cancers were accurately reported. Age at diagnosis was accurate within 5 years for 60% of LFS relatives and 53% of HBOCS relatives. Factors correlating with accurate reporting of cancer history included: being member of BRCA1 family, higher education level, female historian, degree of closeness to affected relative, and having fewer than 5 affected FDRs and SDRs. Relying on verbal histories would not have altered eligibility for genetic testing among HBOCS historians, but fewer than half of LFS historians provided information that would have led to TP53 testing. Our data suggest that it may not be necessary to confirm breast cancer diagnoses routinely; however, documentation of other cancer types remains important for appropriate risk assessment and follow-up.
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PMID:Accuracy of cancer family histories: comparison of two breast cancer syndromes. 1572 43

Breast cancer is the most common malignancy which affects women. In 5-10% of all cases, breast cancer presents as a hereditary cancer syndrome. Since 1996, 68 families with suspicion of familial breast cancer have been referred to our department. In 5 of the 68 families (7.4%), the clinical diagnosis was hereditary breast ovarian cancer syndrome. In 17 families (25%), two or more breast cancer cases were present. Mutation screening of BRCA1 and BRCA2 in these families revealed a BRCA1 mutation (185delAG) in one family. Three families (4.4%) had a diagnosis of Li-Fraumeni syndrome and germline mutations in TP53 (Lys292Ile, Pro278Ser and Pro278Thr). Breast cancer occurred in a family with hereditary nonpolyposis colon carcinoma (HNPCC; Lynch syndrome) carrying an MLH1 mutation (IVS17-3G>C). Most of our families (41 families; 60.2%) had only one case with breast cancer or cystic adenoma (or both) and did not need counseling and DNA testing. In summary, in 10 of the 68 families in our series (14.7%), a germline mutation in a breast cancer predisposing gene was detected. Our data show the importance of detailed examination of clinical data, pedigree analyses, and molecular germline diagnostics for the counseling of breast cancer cases.
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PMID:Hereditary breast cancer syndromes in a Turkish population. Results of molecular germline analysis. 1599 73

The genetic aetiology of familial aggregations of breast cancer and sarcomas has been elucidated only in part. In this study, 23 unrelated individuals from families with one case of sarcoma and at least one case of breast cancer were screened for mutations in the TP53, BRCA1 and BRCA2 genes. Families were classified according to their conformity to the criteria defining the Li-Fraumeni syndrome (LFS), Li-Fraumeni-like (LFL) syndrome and hereditary breast/ovarian cancer (HBOC). Germline TP53 mutations were identified in three instances (13%), including one LFS and two LFL families, while none of the non-LFS/non-LFL families had a TP53 mutation. Three cases (13%), including one with a TP53 mutation, carried BRCA2 mutations. Of these, two were observed in LFL/HBOC families and the other one in a non-LFS/non-LFL/HBOC family, while none of the non-HBOC families tested positive. These findings suggest that the screening of BRCA2, in addition to TP53, may be appropriate for the molecular characterisation of breast cancer/sarcoma families, with practical implications for counselling and clinical management.
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PMID:Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families. 1722 68


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