Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nonsteroidal antiestrogen tamoxifen is the most widely used anticancer drug. In women with breast cancer, adjuvant therapy with tamoxifen reduces relapse and improves overall survival. In advanced breast cancer, the response rate is more than 50% in hormonal dependent disease. In women treated with adjuvant tamoxifen the incidence of new primary breast cancers is decreased. This latter observation has led to the initiation of prevention trials. In 1989 the first report from a large prospective randomised trial showed a significant increase of endometrial carcinoma among women treated with adjuvant tamoxifen. This effect may be linked to the somewhat paradoxical estrogenic properties of tamoxifen. The endometrial effects should be considered in the long term use of tamoxifen, and should also be taken into account in the evaluation of the prevention trials. Animal data indicate that tamoxifen can induce tumours in other organ systems, for example the liver, but no increase in primary liver cancer has been reported from the randomised trials. In some of these trials an increase in other gastrointestinal cancers (e.g. colon and gastric carcinoma) has been observed. The mechanism behind this may be different from that of the endometrium. In animal systems, tamoxifen has shown to induce DNA damage, with formation of DNA adducts. The risk of secondary gastrointestinal cancer needs to be further evaluated. The adverse effects of tamoxifen have led to the development of new anti-estrogenic drugs and other estrogen reducing agents (e.g. aromatase inhibitors).
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PMID:Tamoxifen and secondary tumours. An update. 906 22

The majority of tumors from hereditary nonpolyposis colorectal cancer families and a subset of unselected gastrointestinal and endometrial tumors exhibit a microsatellite mutator phenotype (MMP) that leads to the accumulation of hundreds of thousands of clonal mutations in simple repeat sequences. The mutated genes with positive or negative roles in cell growth or survival in aneuploid gastrointestinal cancer (e.g., APC, K-ras, and p53) are less frequently mutated in near-diploid MMP gastrointestinal tumors. These tumors accumulate mutations in other genes, such as DNA mismatch repair hMSH3 and hMSH6, transforming growth factor-beta type II receptor, and BAX. All these genes carry, within their coding sequences, mononucleotide repeats that are preferred targets for the MMP. Endometrial carcinoma is the most common type of extracolonic neoplasia in the hereditary nonpolyposis colorectal cancer syndrome, but the spectrum of its target cancer genes is not well characterized. Here, we report that endometrial cancer of the MMP also accumulates mutations in genes that are typically mutated in gastrointestinal cancer of the mutator pathway, including BAX (55%), hMSH3 (28%), and hMSH6 (17%). We also report the detection of frameshift mutations in caspase-5, a member of the caspase family of proteases that has an (A)10 repeat within its coding region, in MMP tumors of the endometrium, colon, and stomach (28, 62, and 44%, respectively). We therefore suggest caspase-5 as a new target gene in the microsatellite mutator pathway for cancer.
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PMID:Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype. 1038 66

Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.
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PMID:Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). 1732 85

Peutz-Jeghers' syndrome is an uncommon polyposis syndrome characterized by the presence of hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation (especially in the oral-nasal and perianal areas and hands and feet). Inheritance is autosomal dominant, caused by a germline mutation in the STK11 (LKB1) gene. The risk of breast and gastrointestinal cancer is increased in this syndrome. Lynch's syndrome is also known as hereditary non-polyposis colorectal cancer. This syndrome is caused by a mutation in DNA mismatch repair genes and increases the risk of colon and endometrial cancer, as well as that of other neoplasms (ovary, upper urological tract, gastric, small intestine, pancreas, skin and brain). We present the case of a young woman with colorectal cancer and the coexistence of both syndromes. This association has not previously been reported in the literature.
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PMID:[Coexistence of Peutz-Jeghers' syndrome and Lynch's syndrome in the same patient]. 2251 49