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)

Point mutations of KRAS and BRAF genes are thought to be important in carcinogenesis of colon cancer. In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer. However, a consensus has not been established regarding the correlation between point mutations of KRAS or BRAF and carcinogenesis in patients with endometrial cancer, which is closely related to colon cancer. Therefore, we analyzed aberrant hypermethylation of the hMLH1 gene, microsatellite instability (MSI), and point mutations of KRAS and BRAF in 44 samples of sporadic endo-metrial cancer, with the aim of examining the mechanism of carcinogenesis in patients with endometrial cancer. Aberrant hMLH1 hypermethylation was found in 17 of the 44 cases (38.6%) and showed a significant positive correlation with MSI (p=0.02). This suggests that an abnormal MMR mechanism plays an important role in carcinogenesis of sporadic endometrial cancer. Point mutation of KRAS was found in 6 of the 44 cases (13.6%), but no BRAF V600E mutation was detected. These data suggest that the BRAF V600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer. This is supported by the relatively few previous reports indicating a correlation between endometrial cancer and the BRAF V600E mutation. Identification of new candidates for the target gene for abnormal MMR in endometrial cancer requires further work.
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PMID:Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer. 1942 71

We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister's colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified.
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PMID:Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for Lynch syndrome. 1967

Transplantation of cryopreserved tissue from patients with cancer may carry the risk of reactivation or redissemination of micrometastases. This prospective study was conducted to evaluate the potential involvement of micrometastases in ovarian tissue in cancer patients. Ovarian biopsies were collected from patients who underwent ovarian tissue cryopreservation, in our IVF unit before chemotherapy between 2000 and 2008. Indications for cryopreservation included breast cancer (n=13), osteosarcoma (n=13), hematologic malignancies (n=13), uterine cervix carcinoma (n=2), endometrial carcinoma (n=1), colon cancer (n=1), and brain medulloblastoma (n=1). The samples were stained with hematoxylin and eosin, and examined histologically. Immunoperoxidase broad-spectrum cytokeratin staining was also performed on specimens from breast cancer patients. There were 44 patients (age range 5-40 yr) who yielded 40 specimens. No gross pathologic involvement was observed, and the histologic examination revealed normal histology with no evidence of metastases. Our findings showed that for the purpose of considering ovarian tissue cryopreservation in cancer patients, the likelihood of microscopic metastases within ovaries of normal appearance is apparently very low. Clarification of the actual risk of ovarian involvement and any subsequent risk of micrometastases and tumor reimplantation requires further investigation.
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PMID:Histologic evaluation of fresh human ovarian tissue before cryopreservation. 1995 43

Epidemiological studies have provided convincing evidence that obesity increases the risk for cancers of the oesophagus (adenocarcinoma), colon, pancreas, breast (post-menopausal), endometrium and kidney. The magnitude of the increase in risk varies between cancer sites. For an increase in BMI of 10 kg/m2 relative risks are approximately 2.3 for adenocarcinoma of the oesophagus, 1.5 for colon cancer in men, 1.2 for colon cancer in women, 1.4 for post-menopausal breast cancer, 2.9 for endometrial cancer and >1.5 for kidney cancer, while the size of the effect on cancer of the pancreas is uncertain. There is also evidence that obesity increases the risks for cancers of the gallbladder, malignant melanoma, ovary, thyroid, non-Hodgkin lymphoma, multiple myeloma and leukaemia. Estimates of the percentage of cancers that can be attributed to excess body weight suggest that in the UK and similar countries approximately 5% of all cancers are attributable to overweight and obesity.
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PMID:Symposium 1: Overnutrition: consequences and solutions. Obesity and cancer risk. 1995 65

The risk of endometrial cancer (EC) subsequent to a diagnosis of colorectal cancer in women with a germline mutation in a mismatch repair gene [Lynch syndrome or hereditary non-polyposis colon cancer (HNPCC)] is unknown. We estimated the risk of EC following a diagnosis of colorectal carcinoma (CRC) for women with Lynch syndrome. A retrospective cohort study was performed on women diagnosed with CRC with a germline mutation in a mismatch repair (MMR) gene (Lynch syndrome cases), and women with microsatellite stable (MSS) CRC who were not known to carry a germline mutation (non-Lynch cases), identified from the Colon Cancer Family Registry. The incidence of EC following CRC was estimated and compared for women with and without Lynch syndrome, using adjusted hazards ratios calculated for time at risk among each group. A total of 112 women with Lynch syndrome and a previous diagnosis of CRC were compared with 908 women without Lynch and with a MSS CRC diagnosis. The estimated 10-year cumulative risk of EC subsequent to CRC was 23.4% [95% confidence interval (CI): 15-36%] for Lynch syndrome women compared with 1.6% (95% CI: 0.7-3.8%) for non-Lynch women. After adjusting for ascertainment, age at diagnosis and diagnosis of other cancers, risk of subsequent diagnosis with EC was elevated sixfold in women with Lynch syndrome compared with non-Lynch women (HR 6.2; 95% CI 2.2-17.3; p = 0.001). Approximately one quarter of women diagnosed with Lynch syndrome-associated CRC developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women.
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PMID:Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. 2053 84

Cancer risks for a person who has inherited a MUTYH mutation from only one parent (monoallelic mutation carrier) are uncertain. Using the Colon Cancer Family Registry and Newfoundland Familial Colon Cancer Registry, we identified 2,179 first- and second-degree relatives of 144 incident colorectal cancer (CRC) cases who were monoallelic or biallelic mutation carriers ascertained by sampling population complete cancer registries in the United States, Canada and Australia. Using Cox regression weighted to adjust for sampling on family history, we estimated that the country-, age- and sex-specific standardized incidence ratios (SIRs) for monoallelic mutation carriers, compared to the general population, were: 2.04 (95% confidence interval, CI 1.56-2.70; p < 0.001) for CRC, 3.24 (95%CI 2.18-4.98; p < 0.001) for gastric cancer, 3.09 (95%CI 1.07-12.25; p = 0.07) for liver cancer and 2.33 (95%CI 1.18-5.08; p = 0.02) for endometrial cancer. Age-specific cumulative risks to age 70 years, estimated using the SIRs and US population incidences, were: for CRC, 6% (95%CI 5-8%) for men and 4% (95%CI 3-6%) for women; for gastric cancer, 2% (95%CI 1-3%) for men and 0.7% (95%CI 0.5-1%) for women; for liver cancer, 1% (95%CI 0.3-3%) for men and 0.3% (95%CI 0.1-1%) for women and for endometrial cancer, 4% (95%CI 2-8%). There was no evidence of increased risks for cancers of the brain, pancreas, kidney, lung, breast or prostate. Monoallelic MUTYH mutation carriers with a family history of CRC, such as those identified from screening multiple-case CRC families, are at increased risk of colorectal, gastric, endometrial and possibly liver cancers.
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PMID:Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. 2117 Oct 15

Since the Women's health Initiative (WHI) study published in 2002, hormonal replacement therapy (HRT) prescription is discussed, especially concerning the risk of cancer, and breast cancer in particular. This calling into question led France to publish in 2004 ANAES and AFFAPS recommendations. From recent literature data published by the EMAS, the North American Society and CNGOF, this study aim to discuss cancer risk under HRT. The relative risk (RR) of breast cancer varies from 1.26 in the WHI study to 1.66 in the Million Women Study, with different results according to the interval between menopause and starting hormone therapy and the modalities of HRT (different data for estrogen-only hormone therapy, or within the type of progestogen used). However, impact of breast cancer decreases since 2004, in which role of HRT is difficult to specify. Part of HRT in ovarian cancer is controversial, data being discordant in recent studies and mainly involving estrogen-only hormone therapy. Regarding protective property in endometrial cancer, the dose and duration of progestogen therapy seem to be the main factors. At last, there is no evidence as regards the role of HRT in drop of colon cancer incidence or increased mortality by pulmonary cancer. These updates data must be part of patient information before introducing HRT, in order to get the best evaluation of individual risk and benefit of this treatment.
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PMID:[Menopause and oncologic risks]. 2306 39

Lynch syndrome is the most common inherited colon cancer susceptibility syndrome. Lynch syndrome is characterized by a significantly increased risk for colon cancer and endometrial cancer and a smaller risk for several other associated cancers. Some periodic screening strategies, such as colonoscopy, reduce the incidence and mortality of Lynch syndrome. The aim of this review is to discuss the risks, surveillance tests and guidelines for the management of colonic and extracolonic tumors associated with Lynch syndrome. For extracolonic cancer, a benefit of surveillance is evident only for endometrial cancer. No definitive data show efficacy of chemopreventive drugs, although aspirin is a promising drug. In this review, the available evidence on the different screening strategies in Lynch syndrome will be discussed. Furthermore, the clinical and biological characteristics of this disease and their potential impact on prevention in individuals at risk are analyzed.
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PMID:Follow-up recommendations and risk-reduction initiatives for Lynch syndrome. 2317 23

We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks at the age of 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, respectively, were estimated to be 34% (25%-50%) and 47% (36%-60%) for male carriers and 36% (25%-51%) and 37% (27%-50%) for female carriers. Corresponding EC risks were 18% (9.1%-34%) and 30% (18%-45%). A high level of CRC risk heterogeneity was observed (P < 0.001), with cumulative risks at the age of 70 years estimated to follow U-shaped distributions. For example, 17% of male MSH2 mutation carriers have estimated lifetime risks of 0%-10% and 18% have risks of 90%-100%. Therefore, average risks are similar for the two genes but there is so much individual variation about the average that large proportions of carriers have either very low or very high lifetime cancer risks. Our estimates of CRC and EC cumulative risks for MLH1 and MSH2 mutation carriers are the most precise currently available.
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PMID:Cancer risks for MLH1 and MSH2 mutation carriers. 2325 16

The appearance of endometrial cancer in adolescence is uncommon and warrants investigation for an hereditary cancer syndrome. Cowden syndrome is an autosomal dominant cancer syndrome associated with a germline PTEN mutation and increased risk of breast, thyroid, endometrial and colon cancer. In this report we present a case of a 14-year-old nulligravid female diagnosed with grade 1 endometrial adenocarcinoma. She subsequently developed fibrocystic breast disease and colon polyps and was diagnosed with Cowden syndrome at age 20. We therefore recommend formal evaluation for Cowden syndrome to be considered when endometrial cancer is diagnosed in adolescence.
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PMID:Endometrial cancer in a 14-year-old girl with Cowden syndrome: a case report. 2327 35


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