HNF1B polymorphism influences the prognosis of endometrial cancer patients: a cohort study.
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ABSTRACT:
SUBMITTER: Mandato VD
PROVIDER: S-EPMC4403886 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
HNF1B polymorphism influences the prognosis of endometrial cancer patients: a cohort study.
Mandato Vincenzo Dario VD Farnetti Enrico E Torricelli Federica F Abrate Martino M Casali Bruno B Ciarlini Gino G Pirillo Debora D Gelli Maria Carolina MC Nicoli Davide D Grassi Mario M LA Sala Giovanni Battista GB Palomba Stefano S
BMC cancer 20150407
<h4>Background</h4>HNF1B (formerly known as TCF2) gene encodes for a transcription factor that regulates gene expression involved in normal mesodermal and endodermal developments. A close association between rs4430796 polymorphism of HNF1B gene and decreased endometrial cancer (EC) risk has been demonstrated. The aim of the current study was to test the hypothesis that rs4430796 polymorphism can influence the prognosis of EC patients.<h4>Methods</h4>Retrospective cohort study. Clinical and patho ...[more]
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Project description:We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ? 0.21) or between studies (P ? 0.70). The OR(per allele) was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6)) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7)) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P ? 0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.
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Project description:BackgroundRecent genome-wide association studies (GWAS) have identified many SNPs associated with type 2 diabetes mellitus (T2DM). However, the functional roles for most of the SNPs have not been elucidated. MicroRNAs (miRNAs) are key regulators of gene expression involved in the development and progression of various diseases including T2DM. In this study, we investigated whether commonly occurring SNPs modulate miRNA-directed regulation of gene expression, and whether such SNPs in miRNA-binding sites are associated with the susceptibility for T2DM.MethodsGenotypes of eleven 3' untranslated region (UTR) SNPs of seven susceptibility genes for T2DM were determined in 353 T2DM patients and 448 control subjects. In addition, the interactions of miRNAs with the 3'UTR in the hepatocyte nuclear factor 1β (HNF1B) gene were investigated using luciferase reporter assays.ResultsOne 3'UTR SNP (rs2229295) in the HNF1B gene was significantly associated with T2DM, and the frequency of an A allele (rs2229295) in T2DM patients was decreased compared with that in controls. Luciferase reporter assays showed that the SNP (rs2229295) altered the binding of two miRNAs (hsa-miR-214-5p and hsa-miR-550a-5p).ConclusionsWe have detected the interactions of hsa-miR-214-5p/hsa-miR-550a-5p and the 3'UTR SNP of the HNF1B gene by in vitro luciferase reporter assays, and propose that the binding of such miRNAs regulates the expression of the HNF1B gene and the susceptibility of T2DM.
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Project description:BackgroundThe staging system for patients with anaplastic thyroid cancer (ATC) was updated in the 8th edition of the American Joint Committee on Cancer Staging Manual. A cut-off age of 55 years was stipulated as a prognostic factor for differentiated thyroid cancer; however, age was not considered for ATC patients. To this end, this study investigated the relationship between age at diagnosis and prognosis of ATC patients.MethodsThe clinical information on ATC patients was acquired from the Surveillance, Epidemiology, and End Results Program public database. Youden's index and X-tile analyses were used to calculate the high-point age at diagnosis associated with prognosis. Cox proportional hazards models, Kaplan-Meier curves, and 1000-person-year were then used for verifying the accuracy of the high-point age.ResultsAfter inclusion/exclusion criteria was applied, 586 patients were included in this study. The high-point age was determined to be 70 years by both the Youden's index and X-tile plot methods. The hazard ratio was 1.662 (95% confidence interval [CI]: 1.321-2.092), indicating that there was an increased risk of poor prognosis for patients > 70 years of age. The cancer-specific mortality rates per 1000-person-years for patients ≤ and > 70 years-old were 949.980 (95% CI: 827.323-1090.822) and 1546.667 (95% CI: 1333.114-1794.428), respectively. P-values were < 0.001 for the results shown above.ConclusionOur study found that age influenced the prognosis of ATC patients. Furthermore, we determined that the high-point age at diagnosis was 70 years and that > 70 years of age was associated with a poor prognosis. These results provide a useful addition to the staging manual and can improve the diagnosis, treatment strategies and prognosis of ATC patients.
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Project description:We aim to compare endometrial cancer survival in women with or without histological proven endometriosis or adenomyosis. We identified all women with endometrial cancer between 1990 and 2015 from the Netherlands Cancer Registry (NCR). Data were linked to the Dutch pathology database (PALGA) to select all women with histological proven endometriosis/adenomyosis. Overall survival was compared between women with endometrial cancer with or without endometriosis/adenomyosis. We used multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs). We included 1701 women with endometrial cancer and endometriosis/adenomyosis, of whom 1236 (72.7%) women had adenomyosis, 320 (18.8%) had endometriosis and 145 (8.5%) had both. We compared these women to 39 139 women with endometrial cancer without endometriosis/adenomyosis. Women in the combined endometriosis/adenomyosis cohort were younger at endometrial cancer diagnosis, had earlier disease stage, more often had endometrioid endometrial cancer and low grade tumors. The 5-year survival rate in the combined endometriosis/adenomyosis cohort was 84.8% (95% CI 84.6-88.1) and 71.6% (95% CI 71.1-72.0) in the nonendometriosis/adenomyosis cohort. Univariable analysis resulted in a crude HR of 0.63 (95% CI 0.59-0.69). Significant confounding factors were age, stage, cancer subtype, histological grading, surgery and chemotherapy rate. Correction for these confounders resulted in a HR of 0.98 (95% CI 0.90-1.06). Including endometriosis/adenomyosis status as a categorical factor resulted in similar HRs. In conclusion, women with endometrial cancer and histologically proven endometriosis/adenomyosis have a better overall survival when compared to women with endometrial cancer without endometriosis/adenomyosis. This better survival was correlated to stage, grade, age and histological subtype, but not to the presence of endometriosis/adenomyosis.
| S-EPMC9303796 | biostudies-literature
Project description:BackgroundThe prognosis of recurrent low-grade endometrial stromal sarcoma (LGESS) is little known. This study was to investigate the survival outcomes of a cohort of patients with recurrent LGESS.MethodsPatients with primary LGESS diagnosed and treated for first recurrence confirmed by histology in the study center from February 2012 to June 2019 were retrospectively included. The progression-free interval (PFI) after the last treatment for first recurrence and overall survival (OS) since the diagnosis of first recurrence, which were followed up to June 1, 2020, were compared between groups of various therapy modalities.ResultsFifty-six patients were included, and 43 patients (76.8%) had definite follow-up outcomes. The 5-year PFI and OS rates were 30.0% (95% confidence interval [95% CI] 29.2-30.8) and 75.0% (68.0-82.0), respectively. In univariate analysis, only fertility-sparing treatment, ovarian preservation and surgical treatment had a significant impact on the PFI (hazard ratio [HR] 4.5, 3.1, and 0.2; 95% CI 1.5-13.1, 1.3-7.3, and 0.1-0.7; and p = 0.006, 0.009 and 0.006, respectively), but no factor was found to be associated with increased mortality risk. After adjusted with hormone treatment or chemotherapy, surgical treatment had significant effectiveness on OS (HR 0.3 and 0.3, 95% CI 0.1-1.0 and 0.1-1.0, p = 0.045 and 0.049, respectively). None of the patients with fertility-sparing treatment had successful conception, and all experienced repeated relapse.ConclusionFor patients with recurrent LGESS, fertility-sparing treatment or ovarian preservation should not be provided. Surgery is the treatment of choice, and hormone treatment and/or chemotherapy was effective for the survival benefits of surgical treatment.
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Project description:BackgroundDespite the high prevalence of adenomyosis in hysterectomy specimens of endometrial carcinoma (EC) patients, the relationship between adenomyosis and EC prognosis appears unclear.ObjectiveTo assess the prognostic value of coexistent adenomyosis in patients with EC.MethodsA systematic review and meta-analysis was performed by searching six electronic databases for studies reporting data on prognosis of EC patients with and without coexistent adenomyosis. Studies with patient selection based on prognostic factors were excluded. Pooled univariate hazard ratio (HR) analyses for overall survival (OS) and disease-free survival (DRF) were performed, using EC patients without adenomyosis as a control group. For DFS, pooled multivariate HR analysis was also evaluable.ResultsThree studies of 2505 EC patients (553 with and 1952 without adenomyosis) were included. Compared with EC patients without adenomyosis, EC patients with coexistent adenomyosis showed a pooled HR of 0.533 (CI 95%, 0.329-0.864) for OS at univariate analysis; 0.536 (CI 95%, 0.334-0.859) for DFS at univariate analysis; and 0.875 (CI 95%, 0.331-2.315) for DFS at multivariate analysis.ConclusionIn EC patients with coexistent adenomyosis, the risk of death is halved compared with EC patients without adenomyosis. However, the independence of this association needs to be verified in future studies.
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Project description:Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.
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Project description:ObjectiveTo explore the association between pregnancy duration and risk of endometrial cancer.DesignNationwide register based cohort study.SettingDenmark.ParticipantsAll Danish women born from 1935 to 2002.Main outcome measuresRelative risk (incidence rate ratio) of endometrial cancer by pregnancy number, type, and duration, estimated using log-linear Poisson regression.ResultsAmong 2?311?332 Danish women with 3?947?650 pregnancies, 6743 women developed endometrial cancer during 57?347?622 person years of follow-up. After adjustment for age, period, and socioeconomic factors, a first pregnancy was associated with a noticeably reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk 0.53 (95% confidence interval 0.45 to 0.64) or childbirth (0.66, 0.61 to 0.72). Each subsequent pregnancy was associated with an additional reduction in risk, whether it ended in induced abortion (0.81, 0.77 to 0.86) or childbirth (0.86, 0.84 to 0.89). Duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity, and socioeconomic factors did not modify the results.ConclusionsThe risk of endometrial cancer is reduced regardless of whether a pregnancy ends shortly after conception or at 40 weeks of gestation. This reduction in risk could be explained by a biological process occurring within the first weeks of pregnancy, as pregnancies ending in induced abortions were associated with similar reductions in risk as pregnancies ending in childbirth.
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Project description:Purpose: The efficacy of immunomodulators in improving pregnancy outcomes in infertile patients is controversial, with some reports finding improvements in pregnancy outcomes and some studies finding lack of efficacy in unselected patient populations. Therefore, the aim of this study was to identify people who could benefit from immunotherapy. Methods: 29 patients who had at least one previous embryo transfer failure and planned to undergo another frozen-thawed embryo transfer (FET) cycle were included. Peripheral blood of the patients was collected for detection of serum cytokines, T cell subsets at D3-D9 days of menstrual cycle before FET, mRNA was extracted from endometrial tissues during the window of implantation (WOI) for analysis. All patients began treatment with immunomodulators, including prednisone, hydroxychloroquine, cyclosporine, on the first day of the FET cycle. They were divided into pregnant group and non-pregnant group according to clinical pregnancy. Results: There were no differences in cytokines and T cell subsets between the two groups. Functional annotation of endometrial mRNA revealed functional enrichment in leucocyte mediated immunity, innate immune response, regulation of T cell receptor (TCR) signaling, T cell activation and positive T cell selection. Conclusion: The cytokines and immune cell subsets of peripheral blood cannot accurately predict the outcome of pregnancy after immunotherapy, and endometrial biopsy on the WOI may be a target to identify people who benefit from immunotherapy.
2024-09-09 | GSE272778 | GEO