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      Association between metabolic syndrome and endometrial cancer risk: a systematic review and meta-analysis of observational studies

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          Abstract

          Existing evidence has revealed inconsistent results on the association between metabolic syndrome (MetS) and endometrial cancer (EC) risk. Herein, we aim to better understand this association. Systematic searches of PubMed, EMBASE, and Web of Science through 12 December 2019 were conducted. Observational studies that provided risk estimates of MetS and EC risk were eligible. The quality of the included studies was judged based on the Newcastle–Ottawa scale. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Six studies, comprising 17,772 EC cases and 150,371 participants were included. MetS, diagnosed according to the criteria of the National Cholesterol Education Program—Third Adult Treatment Panel, was associated with an increased risk of EC (OR: 1.62; 95% CI = 1.26–2.07) with substantial heterogeneity (I 2 = 78.3%). Furthermore, we found that women with MetS, diagnosed according to the criteria of the International Diabetes Federation, had a significantly higher risk of EC compared to healthy controls (OR: 1.45; 95% CI = 1.16–1.81; I 2 = 64.6%). Our findings were generally consistent with the main results in the majority of prespecified subgroups, as well as in sensitivity analyses. In conclusion, MetS is associated with EC risk.

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          Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis.

          Diabetes mellitus appears to be a risk factor for some cancers, but the effect of preexisting diabetes on all-cause mortality in newly diagnosed cancer patients is less clear. To perform a systematic review and meta-analysis comparing overall survival in cancer patients with and without preexisting diabetes. We searched MEDLINE and EMBASE through May 15, 2008, including references of qualifying articles. English-language, original investigations in humans with at least 3 months of follow-up were included. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Of 7858 titles identified in our original search, 48 articles met our criteria. One reviewer performed a full abstraction and other reviewers verified accuracy. We contacted authors and obtained additional information for 3 articles with insufficient reported data. Studies reporting cumulative survival rates were summarized qualitatively. Studies reporting Cox proportional hazard ratios (HRs) or Poisson relative risks were combined in a meta-analysis. A random-effects model meta-analysis of 23 articles showed that diabetes was associated with an increased mortality HR of 1.41 (95% confidence interval [CI], 1.28-1.55) compared with normoglycemic individuals across all cancer types. Subgroup analyses by type of cancer showed increased risk for cancers of the endometrium (HR, 1.76; 95% CI, 1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95% CI, 1.24-1.41). Patients diagnosed with cancer who have preexisting diabetes are at increased risk for long-term, all-cause mortality compared with those without diabetes.
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            Type I and II endometrial cancers: have they different risk factors?

            Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m(2) increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.
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              Diabetes mellitus and risk of endometrial cancer: a meta-analysis.

              Diabetes has been associated with a statistically significantly increased risk of endometrial cancer in most, but not all studies. To provide a quantitative assessment of the association between diabetes and risk of endometrial cancer, we conducted a meta-analysis of case-control studies and cohort studies. We identified studies by a literature search of PubMed and Embase through to January 2007 and by searching the reference lists of relevant articles. Summary relative risks (RRs) with 95% CIs were calculated using random-effects model. The analysis of diabetes (largely type 2) and endometrial cancer is based on 16 studies (three cohort and 13 case-control studies), including 96,003 participants and 7,596 cases of endometrial cancer. Twelve of the studies showed a statistically significantly increased risk and four a non-significant increased risk of endometrial cancer. In our meta-analysis we found that diabetes was statistically significantly associated with an increased risk of endometrial cancer (summary RR 2.10, 95% CI 1.75-2.53). The risk estimates were somewhat stronger among case-control (RR 2.22, 95% CI 1.80-2.74) than among cohort studies (RR 1.62, 95% CI 1.21-2.16), stronger among studies adjusting only for age (RR 2.74, 95% CI 1.87-4.00) compared with multivariate adjustment (RR 1.92, 95% CI 1.58-2.33) and slightly lower in studies performed in the USA than in those performed Europe. The analysis of type 1 diabetes and endometrial cancer was based on three studies and found a statistically significant positive association (summary RR 3.15, 95%CI 1.07-9.29). Results from the meta-analysis support a relationship between diabetes and increased risk of endometrial cancer.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                31 May 2020
                22 May 2020
                : 12
                : 10
                : 9825-9839
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
                Author notes
                Correspondence to: Song Gao; email: gaos@sj-hospital.org
                Article
                103247 103247
                10.18632/aging.103247
                7288955
                32439832
                5863ad65-ec82-4592-b303-2aba671390a9
                Copyright © 2020 Wang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 January 2020
                : 20 April 2020
                Categories
                Research Paper

                Cell biology
                endometrial cancer,metabolic syndrome,meta-analysis,risk
                Cell biology
                endometrial cancer, metabolic syndrome, meta-analysis, risk

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