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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of the etiology, early detection, and prevention of breast cancer reported in the past year are reviewed in this paper. Studies of the etiology of breast cancer include reports on genetic and environmental factors. A major advance in the study of inherited forms of breast and ovarian cancer occurred with the identification of the BRCA1 gene. A second breast cancer susceptibility gene, the BRCA2 gene, was localized to chromosome 13q12-13. Multiple mutations in the BRCA1 gene have been identified, presenting a challenge for the development of predictive testing. Controversy continues over the association between hormone replacement therapy and the development of breast cancer. A study of exercise suggests a strong protective effect against the development of early onset breast cancer. Recent studies have failed to find a strong link between dietary fat intake and the development of breast cancer. A meta-analysis of studies of the efficacy of screening for the prevention of breast cancer mortality demonstrates a significant reduction in mortality among women 50 years of age and older. A lowering of breast cancer mortality for women aged 40 to 49 was only demonstrated after 10 to 12 years of follow-up. The risks and benefits of tamoxifen therapy, a potential breast cancer chemoprevention agent, continue to be clarified. Adverse effects on the endometrium, including an increased risk of endometrial cancer, have been reported. Beneficial effects include an improved cardiovascular risk profile and preservation of bone mineral density among postmenopausal women.
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PMID:Epidemiology, prevention, and early detection of breast cancer. 854 94

Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women have been randomized to these trials, and it should be possible, by the year 2000, to detect any preventive effect of tamoxifen in healthy women. Furthermore, with the large numbers of women involved, it should be possible to evaluate prevention in subgroups of participants according to risk of the disease, particularly those women carrying high-risk genes, such as BRCA1 and BRCA2. Adverse effects of tamoxifen have been identified, including a transient bone loss in premenopausal women and uterine effects, including polyps, cysts, and endometrial cancer, in postmenopausal women. Although the potential benefit of tamoxifen in preventing breast cancer in healthy women is likely to outweight any potential long-term risks, the use of other tamoxifen-like drugs, such as raloxifene (Evista) and toremifene (Fareston) is now being investigated.
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PMID:Status of antiestrogen breast cancer prevention trials. 955 88

Genetic instability of microsatellite repeat sequences [microsatellite instability (MI)] is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is a result of inactivating mutations in any of several genes involved in a particular pathway of DNA mismatch repair. Sporadic (i.e., nonhereditary) manifestations of several tumor types, including colorectal, gastric, and endometrial carcinomas, also exhibit MI in a significant fraction of cases. Many MI+ sporadic colorectal carcinomas are associated with somatic mutations of mismatch repair genes, and several genes with coding region microsatellites are frequently mutated as a result in these cancers. The molecular causes and consequences of MI in sporadic endometrial carcinomas remain obscure, however. The aims of this study were: (a) to identify a series of sporadic endometrial carcinomas with clear evidence of MI; (b) to determine the extent to which somatic alterations in mismatch repair genes are associated with this MI; and (c) to establish whether the genes containing coding region microsatellite repeats that are known to be disrupted in MI+ gastrointestinal cancers are also disrupted in MI+ endometrial carcinomas. Matched pairs of normal and tumor DNA from 57 consecutive cases of endometrial carcinoma were examined for evidence of MI using a consensus panel of microsatellite markers. Fourteen cases (25%) displayed unequivocal evidence of MI, consistent with previously published estimates of the incidence of MI+ sporadic endometrial carcinoma. These cases were subjected to a mutation screen of the coding regions and exon-intron boundaries of the mismatch repair genes MSH2 and MLH1. Although several polymorphisms were detected, no clearly deleterious mutations were found in either of these genes. Notably, however, hypermethylation of the MLH1 promoter region was identified in 10 of 14 (71%) MI+ cases. Somatic mutations in coding region microsatellite repeats in the TGFbetaIIR, IGFIIR, BAX, E2F4, MSH3, MSH6, BRCA1, and BRCA2 genes were generally rare. Four MI+ tumors (29%) contained somatic mutations in the PTEN gene, only one of which was likely the result of MI. These data indicate that somatic mutational inactivation of known mismatch repair genes does not account for the great majority of sporadic endometrial carcinomas with MI and that a significant fraction of these cases may instead be causally associated with hypermethylation of the MLH1 promoter. Furthermore, genes with coding region microsatellites that are frequently mutated in MI+ gastrointestinal cancers are rarely mutated in MI+ endometrial cancers, implying the existence of alternative molecular targets for the tumorigenic effects of MI in this tumor type.
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PMID:Causes and consequences of microsatellite instability in endometrial carcinoma. 992 63

We have investigated frameshift mutations in exonic repeats in the ATR, BRCA1, BRCA2, PTCH, CTCF, Cx26, NuMa and TGFbetaRII genes, using human tumor samples from stomach, esophagus, breast and skin and melanoma, as well as colon cancer and endometrial cancer cell lines (125 samples in total). We developed a sensitive method to detect mutations in the repeats, using the introduction of an artificial restriction site into a repeat. The method detects a single mutant among 10(3) normal genes. Thus, an alteration in a repeated sequence can be detected unambiguously. The (A)(8) repeat of BRCA2 was found mutated in only two of five colon cell lines with microsatellite instability (MI(+)). The ATR gene has an (A)(10) repeat which was altered in two of three MI(+) stomach cancer samples and one of three MI(+) endometrial cell lines. The TGFbetaRII gene [with an (A)(10) repeat] had the maximal frequency of mutations: 10 out of 13 MI(+) samples. At least one sample from all types of cancers, except melanomas, was positive for TGFbetaRII gene mutations. No mutations were found in repeats in the BRCA1, PTCH, CTCF, NuMA and Cx26 genes in any types of tumors examined. In conclusion, our study indicates that repeats were altered only in MI(+) cells and that the mutation frequencies in the genes studied differ among tumor types. Based on these results, we discuss meaningful and meaningless alterations in exonic repeats.
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PMID:A novel sensitive method to detect frameshift mutations in exonic repeat sequences of cancer-related genes. 1054 25

Validated quantitative models are available that permit the accurate estimation of a woman's risk of developing invasive breast cancer during a specified period of time. Data from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial indicate that tamoxifen can reduce the risk of developing breast cancer by at least 49% in women who are at increased risk. All premenopausal women whose 5-year risk of developing breast cancer is 1.67% or greater derive a net benefit from taking tamoxifen for risk reduction. Women who have either lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia derive an even greater net benefit. Women who carry mutations in either the BRCA1 or BRCA2 gene will also experience reduced incidence of breast cancer with tamoxifen. Although postmenopausal women derive a net benefit from tamoxifen through the reduction of both breast cancer and bone fracture event rates, the risks of both invasive endometrial cancer and thromboembolic events must be balanced in older women. Physicians should identify appropriate candidates with whom to discuss the possible benefits of tamoxifen for reducing the risk of breast cancer.
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PMID:Reducing the risk of breast cancer with tamoxifen in women at increased risk. 1156 Sep 80

Effectiveness of radiotherapy is influenced by several genetic properties of the targeted cells. The aim of this study was the identification of prognostic indicators of tumor response to radiation in cervical and endometrial cancer. Using microsatellite DNA analysis, we investigated 31 markers, located on 1p, 2p, 2q, 3p, 9p, 9q, 13q, 17p and 17q for genomic alterations in 37 cervical and 21 endometrial cancer cases, with complete follow-up data. Genetic alterations of the initial tumor genotypes were observed after radiation in 86.5% of cervical and 81.0% of endometrial cases. Reversions to the original normal genotype were observed in 40.5 and 28.6% respectively, predominantly in cured patients rather than in recurred cases. Survival curves by the Kaplan-Meier method showed a worse prognosis for cervical cancer patients whose tumors harbor allelic imbalance (AI) on 3p or 13q, and for endometrial cancer patients whose tumors harbor AI on 13q. Our data suggest a possible association of the hMLH1 or BRCA2 genes, implicated in distinct DNA repair pathways and located on 3p and 13q respectively, with response of cervical and endometrial cancer to radiotherapy. Moreover, microsatellite DNA analysis before and after radiation treatment could be used as a marker of the clinical outcome of patients.
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PMID:Allelic imbalance in hMLH1 or BRCA2 loci associated with response of cervical and endometrial cancer to radiotherapy. 1206 Aug 51

About 5% of all ovarian-cancer cases are caused by a genetic predisposition, in particular as a component of the autosomal dominant hereditary breast-ovarian-cancer syndrome. This syndrome is usually due to germline mutations in the BRCA1- or BRCA2-gene. Ovarian and endometrial cancer also occur in families with hereditary non-polyposis colorectal cancer (HNPCC). This syndrome is caused by germline mutations in DNA mismatch-repair genes. Women at high risk of gynaecological cancer based upon familial clustering of disease or a demonstrated pathogenic germ-line mutation are candidates for surveillance: annual gynaecological examinations, including vaginal echoscopy and serum carcinoma antigen CA125 testing. Prophylactic surgery in the form of adnexectomy leads to a marked, but not complete, reduction of ovarian-cancer risk in high-risk cases. There is insufficient evidence to advise against the use of oral contraceptives or hormonal substitution after adnexectomy for healthy women with a genetic predisposition to breast cancer. Recommendations for surveillance and prevention should only be given after genetic-risk counselling, based on a detailed family study and DNA-based diagnosis.
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PMID:[Recommendations for the management of women with an increased genetic risk of gynaecological cancer]. 1251 19

There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone.
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PMID:Germline truncating mutations in both MSH2 and BRCA2 in a single kindred. 1473 97

Pancreatic cancer (PC) is the most fatal of all gastrointestinal cancers, wherein its mortality compares strikingly with its incidence. Unfortunately, 80-90% of PCs are diagnosed in the nonresectable stage. While the lifetime risk of PC in developed countries is approximately 1-3%, it is the fifth most common cause of cancer deaths among both males and females in Western countries. It occurs in excess in Jews. Approximately 5-10% of PC shows familial clustering. Examination of such familial clusters must take into consideration cancers of diverse anatomic sites, such as malignant melanoma in the familial atypical multiple melanoma (FAMMM) syndrome due to the CDKN2A (p16) germline mutation, and combinations of colorectal and endometrial carcinoma, ovarian carcinoma, and several other cancers in hereditary nonpolyposis colorectal cancer (HNPCC), which are due to mismatch repair germline mutations, the most common of which are MSH2 and MLH1 . Other hereditary disorders predisposing to PC include Peutz-Jeghers syndrome, due to the STK11 mutation, familial pancreatitis due to the cationic trypsinogen gene, site-specific familial pancreatic cancer which may be due to the 4q32-34 mutation, hereditary breast-ovarian cancer (HBOC) syndrome that is due to BRCA2 and possibly some families with HBOC that is due to BRCA1 , familial adenomatous polyposis due to the ATP gene, and ataxia telangiectasia due to the ATM germline mutation. This extant heterogeneity mandates that the physician be knowledgeable about these PC-prone syndromes which play such an important role when considering the differential diagnosis of hereditary PC. Unfortunately, there are no PC screening programs with acceptable sensitivity and specificity. However, the gold standard for screening at this time is endoscopic ultrasound. Clearly, there is a great need for the development of novel screening approaches with acceptable sensitivity and specificity. Further research is needed to elucidate those etiologic factors that contribute to the apparent excess of PC in Ashkenazi Jews. Attention should also be given to the search for mutations predisposing to PC in Jews so that opportunities to learn more about the disease's pathogenesis, as well as screening and control, may take place.
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PMID:Familial pancreatic carcinoma in Jews. 1551 47

New insights into the genetic basis of carcinogenesis have been obtained by modern molecular biological techniques. Several susceptibility genes are known. The hereditary breast and ovarian cancer syndrome (germline mutations in BRCA1 and BRCA2) and endometrial cancer in the context of the hereditary non-polyposis colorectal cancer syndrome (HNPCC), germline mutations in mismatch-repair genes, are the most frequent hereditary cancer syndromes in gynaecology. Mutations in TP53 (Li-Fraumeni syndrome) and PTEN (Cowden's disease), associated with increased risk of breast cancer, are responsible for a smaller portion of familial breast cancer. The risk of inheritance and disease can be identified and defined by investigating family history, risk calculation programs, and genetic testing. Afterwards, options of primary, secondary, and tertiary prevention can be formulated. Presently, prophylactic surgery is the only option proven by clinical trials that can reduce the mortality of hereditary breast and ovarian cancer.
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PMID:[Prophylactic surgery of mammary and ovarian carcinoma]. 1623 64


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