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)

Tamoxifen (TAM) is a selective estrogen receptor modulator that is widely used in the prevention and treatment of estrogen receptor-positive (ER(+)) breast cancer. Its use has significantly contributed to a decline in breast cancer mortality, since breast cancer patients treated with TAM for 5 years exhibit a 30-50% reduction in both the rate of disease recurrence after 10 years of patient follow-up and occurrence of contralateral breast cancer. However, in patients treated with TAM there is substantial interindividual variability in the development of resistance to TAM therapy, and in the incidence of TAM-induced adverse events, including deep vein thrombosis, hot flashes, and the development of endometrial cancer. This article will focus on the UDP glucuronosyltransferases, a family of metabolizing enzymes that are responsible for the deactivation and clearance of TAM and TAM metabolites, and how interindividual differences in these enzymes may play a role in patient response to TAM.
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PMID:Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen. 1925 Jan 97

Uridine diphosphate-glucuronosyltransferases (UGTs) are a family of phase II-metabolizing enzymes involved in glucuronic acid conjugation of sex steroid hormones. UGT1A1 and UGT2B7 are expressed in the uterus and involved in the conjugation and elimination of estrogens. Chronic exposure to estrogens is associated with endometrial cancer. Functional polymorphisms have been identified in UGT1A1 and UGT2B7. We hypothesized that these variants may be associated with endometrial cancer risk. We conducted a case-control study nested within the Nurses' Health Study and the Women's Health Study to investigate the associations between five polymorphisms and endometrial cancer risk using 593 invasive endometrial cancer cases and 1545 controls. We did observe the suggestion of an inverse association with homozygote variant carriers of UGT1A1*28 and endometrial cancer risk. We did not observe significant associations between individual single nucleotide polymorphisms and UGT1A1 haplotypes and endometrial cancer risk. Our data suggest that these UGT polymorphisms do not contribute significantly to endometrial cancer risk.
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PMID:Genetic variations in UGT1A1 and UGT2B7 and endometrial cancer risk. 1935 3

Tamoxifen (TAM) is a selective estrogen-receptor modulator that is widely used in the prevention and treatment of estrogen-receptor-positive breast cancer. Its use has significantly contributed to a decline in breast cancer mortality, since breast cancer patients treated with TAM for 5 years exhibit a 30-50% reduction in both the rate of disease recurrence after 10 years of patient follow-up and in the occurrence of contralateral breast cancer. However, in patients treated with TAM, there is substantial interindividual variability in the development of resistance to TAM therapy and in the incidence of TAM-induced adverse events, including deep-vein thrombosis, hot flashes, and the development of endometrial cancer. Aromatase inhibitors (AIs) have emerged as a viable alternative to TAM, working by inhibiting aromatase activity and blocking estrone/estrodiol biosynthesis in postmenopausal women. The current third-generation AIs, anastrozole, exemestane, and letrozole, were used initially for the treatment of metastatic breast cancer, demonstrating similar or greater benefit but less toxicity, compared with TAM, and are now being employed as adjuvant treatment for early breast cancer in postmenopausal women. This article will focus on the UDP-glucuronosyltransferases, a family of metabolizing enzymes that play an important role in the deactivation and clearance of TAM, anastrazole, and exemestane, and how interindividual differences in these enzymes may play a role in patient response to these agents.
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PMID:Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen and aromatase inhibitors. 1982 43