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)

About 40% of French Canadian breast and/or ovarian cancer families harbor germline BRCA1 or BRCA1 mutations where common mutations account for about 84% of all mutations identified in cancer families. Within a series of BRCA1 and BRCA2 mutation-negative families, a germline TP53 13398 G>A (Arg213Gln) mutation was identified, which was selected for mutation analysis in this gene because of a family history consistent with Li-Fraumeni syndrome (LFS). Given the founder effects in this population, the 13398 G>A mutation was screened in series of 52 BRCA1 and BRCA2 mutation-negative cancer families, and a mutation-positive family was identified. However, pedigree inspection and expansion of mutation-positive families with the same mutation revealed that they were closely related to each other. To further characterize the contribution of TP53 in cancer families, mutation analysis was performed in the remaining BRCA1 and BRCA2 mutation-negative cancer families. Thirty sequence variants were identified, the majority of which occur in intronic sequences and are not predicted to affect the functionality of TP53. However, the 14538 G>A (Arg290His) mutation was identified in a family which did not exhibit features consistent with LFS or Li-Fraumeni-like (LFL) syndrome. Neither of the TP53 mutations was detected in 381 French Canadian women with breast cancer diagnosed before 50 years of age not selected for family history of cancer. In all, germline TP53 mutations were identified in two of 52 (3.8%) cancer families, suggesting that TP53 is not a major contributor to BRCA1 and BRCA2 mutation-negative breast and/or ovarian cancer families of French Canadian descent.
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PMID:Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian breast cancer families. 1754 42

Hereditary breast cancer (HBC) accounts for as much as 10% of the total BC burden. Most of these cases will be found to be due to a BRCA germline mutation. An estimated additional 15-20% of those affected with BC will have one or more first- and/or second-degree relatives with BC. Therefore, when these numbers are combined, familial BC risk accounts for approximately 20-25% of the total BC burden. However, because of the often limited information on family history in the etiologic assessment of BC, this may be an underestimate. Confounding factors include its phenotypic and genotypic heterogeneity, given the association of HBC with a plethora of differing cancer syndromes. Its most common occurrence is its association with ovarian cancer in the so-called hereditary breast-ovarian cancer syndrome due to BRCA1 and BRCA2 mutations. More rarely, it occurs in the Li-Fraumeni syndrome, caused by a p53 germline mutation, in which markedly early-onset BC is found in association with brain tumors, sarcomas, leukemia, lymphoma, malignant melanoma, and adrenal cortical carcinoma. Importantly, the age-adjusted incidence of BC in women in the United States fell sharply, by 6.7%, in 2003, when compared with the rate identified in 2002. We postulate that increasing knowledge about the genetics of BC may have partially contributed to the identification of high-risk patients who thereby may have benefited significantly from early diagnosis.
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PMID:Hereditary breast cancer: part I. Diagnosing hereditary breast cancer syndromes. 1808 72

Throughout the past 15 years, the identification of several genes associated with hereditary breast cancer has fueled the growth of clinical genetic counseling and testing services. In addition, increased knowledge of the genetic and molecular pathways of the known hereditary breast cancer genes, as well as an increased understanding of the impact of testing on individuals has added to the ability to identify, manage, and provide psychosocial support for mutation carriers. This review provides an overview of the clinical features, cancer risks, causative genes, and management for hereditary breast and ovarian cancer syndrome, Cowden syndrome, and Li-Fraumeni syndrome. This article summarizes the genetic counseling process and genetic test result interpretation, including a review of the key elements involved in the provision of risk assessment and informed consent, as well as a review of the risks, benefits, and limitations of cancer susceptibility genetic testing.
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PMID:Genetic counseling and testing for common hereditary breast cancer syndromes: a paper from the 2007 William Beaumont hospital symposium on molecular pathology. 1868 97

Magnetic resonance imaging is a major component of breast imaging. Many studies have shown that magnetic resonance imaging is the most sensitive imaging method for detecting invasive breast cancer in comparison with mammography, ultrasound, and clinical breast examinations. Evidence-based clinical indications for breast magnetic resonance imaging include screening patients at high risk for breast cancer, including those with breast/ovarian cancer genes (BRCA1 and BRCA2), those who are untested first-degree relatives of carriers of these genes, those whose lifetime risk of developing breast cancer is 20% to 25% or greater, those who had chest radiation when they were 10 to 30 years old, and those who have or are first-degree relatives of people with Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome. Breast magnetic resonance imaging is performed in conjunction with mammography and does not replace mammography. Outside of the screening population, utilization of breast magnetic resonance imaging for newly diagnosed breast cancer patients and its use as a problem-solving technique for equivocal mammographic or clinical findings remain controversial. An understanding of the current evidence facilitates appropriate utilization of this important medical resource. This article discusses indications for ordering breast magnetic resonance imaging and how to read the breast magnetic resonance imaging report and understand the lexicon used.
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PMID:Breast magnetic resonance imaging: an overview for nonradiologists. 2001 26

A great majority of human cancers encounter disruption of the p53 network. Identification and characterization of molecular components important in both p53-dependent and p53-independent apoptosis might be useful in developing novel therapies. Previously, we reported that concanavalin A (Con A) induced p73-dependent apoptosis of cells lacking functional p53. In the present study, we investigated the mechanism and role of p53 in protection from apoptosis induced by Con A. Treatment with Con A resulted in apoptosis of p53-null ovarian cancer, SKOV3, or Li-Fraumeni syndrome, MDAH041 (041), cells. However, their isogenic pairs, SKP53 and TR9-7, expressing wild-type p53 were much less sensitive and were protected by G(1) arrest. Inhibition of p53 function rendered these cells sensitive to Con A. Con A-induced apoptosis was accompanied by upregulation of forkhead box O1a (FOXO1a) and Bcl-2-interacting mediator (Bim), which were strongly inhibited after p53 expression and rescued after p53 ablation. Moreover, ablation of Bim by short hairpin RNA protected cells from apoptosis. Taken together, our study suggests that Con A induces apoptosis of cells lacking p53 by activating FOXO1a-Bim signaling and that expression of p53 protects these cells by inducing G(1) arrest and by downregulating the expression of both FOXO1a and Bim, identifying a novel cross-talk between FOXO1a and p53 transcription factors.
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PMID:Restoration of p53 functions protects cells from concanavalin A-induced apoptosis. 2012 56

Hereditary cancer syndromes are frequently seen in young cancer patients and patients with a positive family history. Genetic testing is important for the identification of high-risk individuals, and for the early introduction of specialized preventive care or prophylactic surgeries. High-risk tumour suppressor genes (BRCA1 and BRCA2) and DNA repair genes (MLH1, MSH2 and MSH6) are responsible for a substantial part of hereditary breast, ovarian and colorectal cancer. Other hereditary cancers are seen less frequently, but genetic testing has increased for many other site-specific cancers and complex syndromes. Genetic centres and molecular genetic laboratories are located mostly within university or regional hospitals. Some genetic centres are private. It is highly recommended (Czech Society for Medical Genetics) that all laboratories are accredited according to ISO 15,189 and that genetic testing of hereditary cancer syndromes is indicated by medical geneticists. The indication criteria and prevention strategies were published in Supplement 22 of Clinical Oncology 2009 (in Czech). Preventive care for high-risk individuals is organized by thirteen Oncology Centres, which provide most of the oncology care in the Czech Republic. Genetic testing and preventive care for high-risk individuals and mutation carriers is covered by health insurance. The molecular genetic laboratory at the MMCI provides molecular genetic testing of BRCA1, BRCA2, CHEK2 for hereditary breast/ovarian cancer, MLH1, MSH2, MSH6 for Lynch syndrome,TP53 for Li-Fraumeni syndrome, CDKN2A for familial malignant melanoma syndrome and CDH1 gene for hereditary diffuse gastric cancer. Other syndromes are tested in specialized laboratories elsewhere.The use of genetic testing is increasing because of more frequent referrals from oncologists and other specialists and the increasing variety of genes tested. However, in some patients the testing is not recommended and other family members are dying because of the late diagnosis of hereditary syndrome. Greater awareness of the importance of genetic testing in oncology is needed.
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PMID:Genetic testing and prevention of hereditary cancer at the MMCI--over 10 years of experience. 2134 12

CHEK2 gene mutations occur in a subset of patients with familial breast cancer, acting as moderate/low penetrance cancer susceptibility alleles. Although CHEK2 is no longer recognized as a major determinant of the Li-Fraumeni syndrome, a hereditary condition predisposing to cancer at multiple sites, it cannot be ruled out that mutations of this gene play a role in malignancies arising in peculiar multi-cancer families. To assess the contribution of CHEK2 to the breast cancer/sarcoma phenotype, we screened for germ-line sequence variations of the gene among 12 probands from hereditary breast/ovarian cancer families with one case of sarcoma that tested wild-type for mutations in the BRCA1, BRCA2, and TP53 genes. Two cases harbored previously unreported mutations in CHEK2, the c.507delT and c.38A>G, leading to protein truncation (p.Phe169LeufsX2) and amino acid substitution (p.His13Arg), respectively. These mutations were not considered common polymorphic variants, as they were undetected in 230 healthy controls of the same ethnic origin. While the c.38A>G encodes a mutant protein that behaves in biochemical assays as the wild-type form, the c.507delT is a loss-of-function mutation. The identification of two previously unreported CHEK2 variants, including a truncating mutation leading to constitutional haploinsufficiency, in individuals belonging to families selected for breast cancer/sarcoma phenotype, supports the hypothesis that the CHEK2 gene may act as a factor contributing to individual tumor development in peculiar familial backgrounds.
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PMID:Two new CHEK2 germ-line variants detected in breast cancer/sarcoma families negative for BRCA1, BRCA2, and TP53 gene mutations. 2156 11

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.
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PMID:Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention. 2186 31

The benefits of a skillful medical history and histologic confirmation of relevant pathology are potentially lifesaving. Appropriately directed DNA testing based on these initial steps provides an opportunity for clinical translation into a cancer prevention program targeted to family members. Unfortunately, cancer prevention strategies that are based on genetics are frequently overlooked or underestimated in the overall practical management of patients at high risk for breast cancer as well as integral cancers that constitute a hereditary breast cancer syndrome. DNA testing, particularly for BRCA1 and BRCA2 in hereditary breast-ovarian cancer syndrome and p53 in the Li-Fraumeni syndrome, and many other syndromes is commercially available for inclusion in a cancer control program and merits attention in this major public health problem. It is clear that the time and effort expended for a hereditary cancer syndrome diagnosis may significantly reduce both morbidity and mortality in breast cancer. We have found that genetic counselors can partner with the clinical physicians and make significant contributions to this labor-intensive effort.
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PMID:Hereditary breast cancer: practical pursuit for clinical translation. 2243 44

Gastric cancer is a global public health concern, ranking as the fourth leading cause of cancer mortality, with a 5-year survival of only 20%. Approximately 10% of gastric cancers appear to have a familial predisposition, and about half of these can be attributed to hereditary germline mutations. We review the genetic syndromes and current standards for genetic counseling, testing, and medical management for screening and treatment of gastric cancer. Recently, germline mutations in the E-cadherin/CDH1 gene have been identified in families with an autosomal dominant inherited predisposition to gastric cancer of the diffuse type. The cumulative lifetime risk of developing gastric cancer in CDH1 mutation carriers is up to 80%, and women from these families also have an increased risk for developing lobular breast cancer. Prophylactic gastrectomies are recommended in unaffected CDH1 mutation carriers, because screening endoscopic examinations and blind biopsies have proven inadequate for surveillance. In addition to this syndrome, gastric cancer risk is elevated in Lynch syndrome associated with germline mutations in DNA mismatch repair genes and microsatellite instability, in hereditary breast and ovarian cancer syndrome due to germline BRCA1 and BRCA2 mutations, in familial adenomatous polyposis caused by germline APC mutations, in Li-Fraumeni syndrome due to germline p53 mutations, in Peutz-Jeghers syndrome associated with germline STK11 mutations, and in juvenile polyposis syndrome associated with germline mutations in the SMAD4 and BMPR1A genes. Guidelines for genetic testing, counseling, and management of individuals with hereditary diffuse gastric cancer are suggested. A raised awareness among the physician and genetic counseling communities regarding these syndromes may allow for increased detection and prevention of gastric cancers in these high-risk individuals.
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PMID:Genetic testing by cancer site: stomach. 2284 38


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