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      Statin use and the risk of ovarian and endometrial cancers: a meta-analysis

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          Abstract

          Background

          The relationship between statin use and the risk of ovarian or endometrial cancer remains controversial. Here, we investigated the relationship between statin use and the risk of ovarian and endometrial cancers.

          Methods

          We conducted a meta-analysis using articles retrieved from the PubMed, Embase, and Web of Science databases. All original comparative studies published in English that were related to statin use and the risk of ovarian or endometrial cancer were included.

          Results

          This meta-analysis included 19 studies enrolling 1,999,362 female subjects and 19,849 cancer cases (7,948 ovarian cancer cases and 11,901 endometrial cancer cases). The overall analysis indicated that statin use did not significantly reduce the risk of ovarian cancer [relative risk (RR) = 0.88, 95% confidence interval (CI) 0.76–1.03, p = 0.12] or the risk of endometrial cancer (RR = 0.88, 95% CI 0.78–1.00, p = 0.05.) Subgroup analyses based on study type, percentage of cancer cases, study location, and quality of studies also supported our conclusions. No association was found between long-term statin use (> 5 years) and the risk of ovarian cancer (RR = 0.73, 95% CI 0.51–1.04, p = 0.08) or endometrial cancer (RR = 0.79, 95% CI 0.58–1.08, p = 0.14).

          Conclusions

          Statin use did not lower the risk of ovarian cancer or endometrial cancer. The long-term use of statins (> 5 years) was not associated with a reduction in the risk of ovarian or endometrial cancer.

          Electronic supplementary material

          The online version of this article (10.1186/s12885-019-5954-0) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          The Wnt/β-catenin pathway in ovarian cancer: a review.

          Ovarian cancer is the deadliest gynecologic malignancy and the fifth leading cause of death from cancer in women in the U.S. Since overall survival remains poor, there is a need for new therapeutic paradigms. This paper will review the Wnt/β-catenin pathway as it relates to epithelial ovarian cancer, specifically its role in chemoresistance and its potential role as a target for chemosensitization. A PubMed search was performed for articles published pertaining to Wnt/β-catenin pathway specific to ovarian cancer. Wnt/β-catenin signaling pathways play an active role in cancer stem cells (CSCs) and carcinogenesis of all ovarian cancer subtypes. Studies also have shown that ovarian CSCs are involved in chemoresistance, metastasis, and tumor recurrence. Wnt/β-catenin target genes regulate cell proliferation and apoptosis, thereby mediating cancer initiation and progression. The Wnt/β-catenin pathway is one of the major signaling pathways thought to be involved in epithelial-to-mesenchymal transition (EMT). Alterations affecting Wnt pathway proteins on the cell membrane, in the cytoplasm, and in the nucleus have been shown to play important roles in the tumorigenesis of ovarian cancer. Wnt signaling is activated in epithelial ovarian cancer. Given the role of the Wnt/β-catenin pathway in carcinogenesis, more pre-clinical studies are warranted to further investigate other Wnt inhibitors in ovarian cancer. The Wnt pathway should also be investigated as a potential target in the development of new drugs for ovarian cancer as a single agent and in combination with chemotherapy or other targeted agents. © 2013.
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            Meta-analysis, funnel plots and sensitivity analysis.

            Publication bias is a major problem, perhaps the major problem, in meta-analysis (or systematic reviews). Small studies are more likely to be published if their results are 'significant' than if their results are negative or inconclusive, and so the studies available for review are biased in favour of those with positive outcomes. Correcting for this bias is not possible without making untestable assumptions. In this paper, a sensitivity analysis is suggested which is based on fitting a model to the funnel plot. Some examples are discussed.
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              Assessing the quality of randomized trials: reliability of the Jadad scale.

              An instrument was developed and validated by Jadad, et al. to assess the quality of clinical trials using studies from the pain literature. Our study determined the reliability of the Jadad scale and the effect of blinding on interrater agreement in another group of primary studies. Four raters independently assessed blinded and unblinded versions of 76 randomized trials. Interrater agreement was calculated among combinations of four raters for blinded and unblinded versions of the studies. A 4 x 2 x 2 repeated measures design was employed to evaluate the effect of blinding. The interrater agreement for the Jadad scale was poor (kappa 0.37 to 0.39), but agreement improved substantially (kappa 0.53 to 0.59) with removal of the third item (an explanation of withdrawals). Blinding did not significantly affect the Jadad scale scores. A more precise description of how to score the withdrawal item and careful conduct of a practice set of articles might improve interrater agreement. In contrast with the conclusions reached by Jadad, we were unable to demonstrate a significant effect of blinding on the quality scores.
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                Author and article information

                Contributors
                wangyz3@sj-hospital.org
                renf@sj-hospital.org
                songzixuan666@163.com
                joyboy125@163.com
                fkzlliushuang@126.com
                +86-24-96615-41111 , ouyl@sj-hospital.org
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                24 July 2019
                24 July 2019
                2019
                : 19
                : 730
                Affiliations
                ISNI 0000 0004 1806 3501, GRID grid.412467.2, Department of Obstetrics and Gynecology, , Shengjing Hospital of China Medical University, ; Shenyang, 110004 People’s Republic of China
                Author information
                http://orcid.org/0000-0001-6551-8773
                Article
                5954
                10.1186/s12885-019-5954-0
                6657066
                31340777
                6d48d839-6c4b-4c08-820f-42d463464f22
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 October 2018
                : 18 July 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81501235
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                statin,ovarian cancer,endometrial cancer
                Oncology & Radiotherapy
                statin, ovarian cancer, endometrial cancer

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