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)

We evaluated the interactive effect of polymorphisms in the sex hormone-binding globulin (SHBG) gene with soy isoflavones, tea consumption, and dietary fiber on endometrial cancer risk in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 controls. Genotyping of polymorphisms was performed by using TaqMan (Applied Biosystems, Foster City, CA) assays (rs6259) or the Affymetrix MegAllele Targeted Genotyping System (Affymetrix, Inc., US) (rs13894, rs858521, and rs2955617). Dietary information was obtained using a validated food frequency questionnaire. A logistic regression model was employed to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found that the Asp(327)Asn (rs6259) polymorphism was associated with decreased risk of endometrial cancer, particularly among postmenopausal women (OR = 0.79, 95% CI = 0.62-1.00). This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at Asp(327)Asn (rs6259), particularly premenopausal women (P(interaction) = 0.06 and 0.02, respectively, for soy isoflavones and tea intake). This study suggests that gene-diet interaction may play an important role in the etiology of endometrial cancer risk.
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PMID:The Asp(327)Asn polymorphism in the sex hormone-binding globulin gene modifies the association of soy food and tea intake with endometrial cancer risk. 1900 73

Autophagy appears to play an important role in the normal development and maintenance of homeostasis in a variety of tissues, including the female reproductive tract. However, the role of autophagy and the association between autophagy and apoptosis in cyclic remodeling of the human endometrium have not been described. Therefore, we investigated the involvement of autophagy during the human endometrial cycle and its association with apoptosis. Endometrial samples were obtained from 15 premenopausal, nonpregnant women who underwent hysterectomies for benign gynecological reasons. The autophagy-associated protein, microtubule-associated protein 1 light chain 3 alpha (MAP1LC3A), was immunolocalized, and its expression level was measured by Western blot analysis. Apoptosis was evaluated by measuring the expression level of cleaved caspase 3 protein. MAP1LC3A protein was primarily expressed within the endometrial glandular cells and increased during the secretory phase. The expression level of the membrane-bound form of MAP1LC3A (MAP1LC3A-II) also increased as the menstrual cycle progressed, reaching a maximum level during the late secretory phase. This pattern coincided with the expression of cleaved caspase 3. Furthermore, expression of MAP1LC3A-II and cleaved caspase 3 increased in the in vitro-cultured endometrial cancer cells when estrogen and/or progesterone were withdrawn from the culture media to mimic physiological hormonal changes. These findings suggest that endometrial cell autophagy is directly involved in the cyclic remodeling of the human endometrium and is correlated with apoptosis. In addition, we inhibited autophagic processes using 3-methyladenine (3-MA) or bafilomycin A1 (Baf A1) to evaluate the role of autophagy in apoptosis induction in endometrial cancer cells. While the inhibition of autophagosome formation using 3-MA did not decrease apoptosis or cell death, the inhibition of autophagosome degradation by fusion with lysosomes using Baf A1 increased apoptosis and cell death, suggesting that the accumulation of autophagosomes induces apoptosis. Furthermore, Baf A1-induced apoptotic cell death was decreased by the apoptosis inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK). In conclusion, these results indicate that autophagy is involved in the endometrial cell cycle affecting apoptosis and is most prominent during the late secretory phase.
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PMID:The role of autophagy in human endometrium. 2208 18

Several polymorphisms in the DNA repair gene are thought to have significant effects on cancer risk. In this study, we investigated the association of the polymorphisms in the DNA repair genes, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys, with endometrium cancer risk. Two hundred and sixty-two women were included in the study. Endometrial biopsy was performed, and on the basis of diagnosis and histological examination, women were divided into two groups: a control group (n=158) and an endometrial cancer group (n=104). Genotypes were determined by PCR-RFLP assays in endometrial carcinoma patients and age-matched controls. In this study, we found that the frequencies of Glu+ and Asp/Glu genotypes in APE, Gln/Gln genotype of XRCC1, Met/Met genotype of XRCC3, Cys+ and Ser/Cys genotypes of HOGG1, His+ and Asp/His genotypes of XPG, and Gln+ and Gln/Gln genotypes of XPD are more prevalent in patients than controls. Frequencies of Thr/Thr genotype in XRCC3 were increased in controls compared with patients and seem to be protected from endometrial cancer. Our findings suggest that XRCC1, XRCC3, XPD, XPG, APE1, and HOGG1 genetic variants may be associated with endometrial cancer in Turkish women.
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PMID:DNA repair gene variants in endometrial carcinoma. 2227 35

Aim: The aim of this study was to analyse the frequencies of genotypes and alleles of Single Nucleotide Polymorphisms (SNPs) of six DNA repair genes (XRCC1-rs25487, XPD-rs13181, hMSH2-rs4987188, XRCC2-rs3218536, BRCA1-rs799917 and BRCA2-rs144848 SNPs) and attempt to evaluate the effect this DNA marker on endometrial cancer (EC). Material and methods: The patients were recruited to the study at the Department of Operative Gynaecology of the Institute of the Polish Mother's Memorial Hospital in Lodz. The study comprised 510 patients treated for EC. 510 disease-free individuals were used as controls. SNPs were analysed by the high resolutionmelting technique (HRM). Results: Statistically significant correlations were identified between four SNPs and endometrial cancer risk: rs25487, rs4987188, rs13181 and rs799917. The alleles XRCC1-Gln (OR 2.89; 95% CI 2.39-3.49, P<0.0001), hMSH2-Asp (OR 1.65; 95% CI 1.38-1.96, P<0.0001), XPD-Gln (OR 3.24; 95% CI 2.69-3.91, P<0.0001) and BRCA1-L (OR 1.56; 95% CI 1.31-1.85, P<0.0001) genes were strongly correlated with this malignancy. No relationship was found between the studied polymorphisms of XRCC2 and BRCA2 and the incidence of endometrial cancer. There was also not any association between polymorphisms of XRCC1, hMSH2, XPD, XRCC2, BRCA1, BRCA2, i.e., the polymorphisms of the analysed repair genes, and the cancer stage progression acc. to FIGO, the body mass index, the number of pregnancies in history, replacement therapy, diabetes mellitus and hypertension. Conclusions: The results indicate that rs25487, rs4987188, rs13181, and rs799917 SNPs may be associated with the incidence of endometrial cancer.
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PMID:Association between single nucleotide polymorphism of DNA repair genes and endometrial cancer: a case-control study. 3193 77

The tumour suppressor gene, PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten), can act as both protein phosphatase and lipid phosphatase, is known to play a vital role in Pi3k signalling pathway. In humans, it is located at 10q23. Loss of its phosphatase and catalytic activity is associated with various types of cancers. This study focuses on evolution, understanding the somatic missense mutation in a particular residue of PTEN and understanding the molecular mechanism that leads to endometrial carcinoma through molecular docking. Mutational analysis of H123 position indicates that the missense mutation at first position of the codon CAC by G or T, result in aspartic acid or tyrosine instead of histidine and can have negative effect on the function of PTEN. Alongside, structural analysis showed mutated PTEN has lower stability than the normal. Additionally, SNPs dataset for endometrial carcinoma suggests H123 as strongly mutated residue. The mutation in phosphatase domain of PTEN along with its effect and interaction with substrate TLA1352 were systematically studied through molecular docking. Molecular interaction study reveals that the optimal substrate binding site in PTEN is unable to interact with the substrate in the mutated condition. This observation drew attention on the impact of mutation on disease biology and enabled us to conduct follow-up studies to retrieve novel molecular targets, such as mutated protein domain and modified Asp and Tyr sites, to design effective therapies to either prevent endometrial carcinoma or impede its progression.
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PMID:Loss of phosphatase activity in PTEN (phosphatase and tensin homolog deleted on chromosome ten) results in endometrial carcinoma in humans: An in-silico study. 3204 34

The ovarian tumor domain (OTU) deubiquitinylating cysteine proteases OTUB1 and OTUB2 (OTU ubiquitin aldehyde binding 1 and 2) are representative members of the OTU subfamily of deubiquitinylases. Deubiquitinylation critically regulates a multitude of important cellular processes, such as apoptosis, cell signaling, and growth. Moreover, elevated OTUB expression has been observed in various cancers, including glioma, endometrial cancer, ovarian cancer, and breast cancer. Here, using molecular dynamics simulation approaches, we found that both OTUB1 and OTUB2 display a catalytic triad characteristic of proteases but differ in their configuration and protonation states. The OTUB1 protein had a prearranged catalytic site, with strong electrostatic interactions between the active-site residues His265 and Asp267 In OTUB2, however, the arrangement of the catalytic triad was different. In the absence of ubiquitin, the neutral states of the catalytic-site residues in OTUB2 were more stable, resulting in larger distances between these residues. Only upon ubiquitin binding did the catalytic triad in OTUB2 rearrange and bring the active site into a catalytically feasible state. An analysis of water access channels revealed only a few diffusion trajectories for the catalytically active form of OTUB1, whereas in OTUB2 the catalytic site was solvent-accessible, and a larger number of water molecules reached and left the binding pocket. Interestingly, in OTUB2, the catalytic residues His224 and Asn226 formed a stable hydrogen bond. We propose that the observed differences in activation kinetics, protonation states, water channels, and active-site accessibility between OTUB1 and OTUB2 may be relevant for the selective design of OTU inhibitors.
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PMID:Activation and selectivity of OTUB-1 and OTUB-2 deubiquitinylases. 3226 97