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 evidence of the effects of combined oral contraceptives (COCs) on mortality and morbidity is reviewed. All the 11 case-control studies published since 1980 reported and approximate halving of endometrial cancer risk among COC users. The CASH study showed that the protective effect was apparent after 12 months' use, and users had 40% of the risk of non-users after 2 years' use. A study showed that 5 patterns of self-perceived prolonged, heavy, frequent, irregular, or painful bleeding during menstruation were reported less frequently in COC users than in users of other methods. Benign breast disease is rarer, and functional ovarian cysts are less frequent in COC users. Lower-dose preparations may carry a lower risk of myocardial infarction. Smoking possibly potentiates the risk associated with oral contraceptive (OC) use, and it is a major risk factor for myocardial infarction. The Oxford/FPA study found a 2-3-fold increase in incidence of non-haemorrhagic stroke among current OC users. The epidemiologic data on the current risk of venous thromboembolism in relation to OC use are equivocal. New lower dose COCs have a smaller adverse effect on the lipid profile: they cause a smaller increase in low density lipoprotein cholesterol (LDL) and a variable but smaller decrease in high density lipoprotein cholesterol (HDL). The large CASH study, based on 2088 cases, found a significantly elevated relative risk (2.7) of breast cancer, but only in women who had used the OC for at least 11 years. Of 6 case-control studies of hepatocellular carcinoma and OC use published since 1983, all but one showed a large elevated relative risk of around 4-fold. Delayed return of fertility has been observed in nulliparous women 30 who had 2 years; continuous exposure to COCs, although this may not be associated with low-dose, modern OCs. Malignant melanoma, pituitary adenoma, gallbladder disease, and chronic inflammatory bowel disease have been possibly associated with adverse side effects, but results are so far inconclusive.
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PMID:Combined oral contraceptives: risks and benefits. 832 3

Pregnane X Receptor (PXR) is a member of the nuclear receptor superfamily, expressed in liver, intestine and other tissues. PXR exerts transcriptional regulation by binding to its DNA response elements as an heterodimer with Retinoid X Receptor (RXR). This nuclear receptor is implicated in the homeostasis of numerous endobiotics, such as glucose, lipids, steroids and bile acids. Additionally, the activation of PXR induces expression of drug metabolizing enzymes (DMEs) and transporters, including multidrug resistance protein 1 (MDR1), leading to regulation of xenobiotic metabolism and drug-drug interactions. New roles for PXR have been established in inflammatory bowel disease, bone homeostasis, liver steatosis, antifibrogenesis and oxidative stress. PXR has, additionally, a multifactorial impact on cancer, either by directly affecting cell proliferation and apoptosis or by inducing chemotherapy resistance, in colon, breast, prostate, and endometrial cancer, and in osteosarcoma. PXR polymorphisms may also have clinical significance in certain types of cancer and their treatment. Further studies are needed in order to clarify the mechanisms involved in PXR-regulated carcinogenesis. PXR down-regulation could be considered as a novel therapeutic approach to overcome chemoresistance, while future research should be mainly focused on modulating PXR status in order to increase chemotherapy effectiveness and finally improve cancer patient prognosis.
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PMID:Pregnane X receptor and human malignancy. 2341 96

Mitochondria are semi-autonomous organelles of eukaryotic cells. They perform crucial functions such as generating most of the cellular energy through the oxidative phosphorylation (OXPHOS) system and some other metabolic processes. In addition, mitochondria are involved in regulation of cell death and reactive oxygen species (ROS) generation. Also, mitochondria play important roles in carcinogenesis via altering energy metabolism, resistance to apoptosis, increase of production of ROS and mtDNA (mitochondrial genome) changes. Studies have suggested that aerobic glycolysis is high in malignant tumors. Probably, it correlates with high glucose intake of cancerous tissues. This observation is contrary to Warburg's theory that the main way of energy generation in cancer cells is non-oxidative glycolysis. Further studies have suggested that in tumor cells both oxidative phosphorylation and glycolysis were active at various rates. An increase of intracellular oxidative stress induces damage of cellular structure and somatic mutations. Further studies confirmed that permanent activity of oxidative stress and the influence of chronic inflammation damage the healthy neighboring epithelium and may lead to carcinogenesis. For instance, chronic inflammatory bowel disease could be related to high risk of colon adenocarcinoma. The data have shown a role of ROS generation, mtDNA or nDNA alterations and abnormal apoptotic machinery in endometrial cancer progress. Recent studies suggest that mtDNA mutations might play a potential role in endometrial cancer progress and indicate an increase of mitochondrial biogenesis in this cancer. The investigators suggested that MtCOI and MtND6 alteration has an influence on assembly of respiratory complexes in endometrial cancer. In many human cancers, there is a deregulation of the balance between cell growth and death. The tumor cells can avoid apoptosis through a loss of balance between anti- and pro-apoptotic proteins, reduced caspase function and impaired death receptor signaling. Over-expression of the anti-apoptotic BCL-2 gene has also been identified in numerous cancers including colon, thyroid, breast and endometrial cancer. Most studies have found low BCL-2 family gene expression, which could be a sign of blocking apoptosis in breast and endometrial cancer. Moreover, BCL-2 gene expression is correlated with the degree of aggressiveness and differentiation in endometrial cancer. As a result, it could be a valuable predictor of disease progression.
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PMID:Mitochondrial dysfunction in cancer. 2632 44

In this review the risk of breast, ovarian, and endometrial cancer and cervical and vulvovaginal (pre)malignant abnormalities in patients with inflammatory bowel disease (IBD) with or without immune suppressive treatment will be discussed. So far, this has not been studied thoroughly and large studies taking into account diverse potential confounding factors are lacking. IBD per se has not been associated with development of cervical cancer, yet patients with Crohn's disease who smoke, have a younger age at diagnosis or who use(d) thiopurines might be more at risk. Other immunosuppressive medication seems not to increase this risk, however, as evidence at this point is incomplete, physician awareness and prevention by lifestyle counseling, HPV vaccination and (intensified) screening are warranted. The risk for breast, endometrial, ovarian, and vulvovaginal cancer in IBD patients appears to be comparable to the background population, although for breast cancer this may even be decreasedin Crohn's disease specifically. Immunosuppressive medication in general does not seem to alter this risk. Earlier and more frequent screening for breast cancer than currently conducted in general nationwide screening programs is not recommended at this moment. Current literature suggests a much lower overall malignancy recurrence rate in IBD patients than has been observed previously. More importantly, immune suppressive medication does not appear to increase the recurrence risk. Robust epidemiologic data on female genital tract cancer are needed.
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PMID:Neoplasia and Precursor Lesions of the Female Genital Tract in IBD: Epidemiology, Role of Immunosuppressants, and Clinical Implications. 2946 89