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Original research
Association between genetic polymorphisms and endometrial cancer risk: a systematic review
  1. Cemsel Bafligil1,
  2. Deborah J Thompson2,
  3. Artitaya Lophatananon3,
  4. Miriam J Smith4,
  5. Neil AJ Ryan1,
  6. Anie Naqvi5,
  7. D Gareth Evans4,
  8. Emma J Crosbie1,6
  1. 1 Division of Cancer Sciences, University of Manchester, Manchester, UK
  2. 2 Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  3. 3 Division of Population Health, University of Manchester, Manchester, UK
  4. 4 Division of Evolution and Genomic Sciences, University of Manchester, Manchester, UK
  5. 5 University of Manchester Medical School, Manchester, UK
  6. 6 Department of Obstetrics and Gynaecology, Manchester University NHS Foundation Trust, Manchester, UK
  1. Correspondence to Dr Emma J Crosbie, Division of Cancer Sciences, University of Manchester, Manchester, UK; emma.crosbie{at}


Introduction Endometrial cancer is one of the most commonly diagnosed cancers in women. Although there is a hereditary component to endometrial cancer, most cases are thought to be sporadic and lifestyle related. The aim of this study was to systematically review prospective and retrospective case–control studies, meta-analyses and genome-wide association studies to identify genomic variants that may be associated with endometrial cancer risk.

Methods We searched MEDLINE, Embase and CINAHL from 2007 to 2019 without restrictions. We followed PRISMA 2009 guidelines. The search yielded 3015 hits in total. Following duplicate exclusion, 2674 abstracts were screened and 453 full-texts evaluated based on our pre-defined screening criteria. 149 articles were eligible for inclusion.

Results We found that single nucleotide polymorphisms (SNPs) in HNF1B, KLF, EIF2AK, CYP19A1, SOX4 and MYC were strongly associated with incident endometrial cancer. Nineteen variants were reported with genome-wide significance and a further five with suggestive significance. No convincing evidence was found for the widely studied MDM2 variant rs2279744. Publication bias and false discovery rates were noted throughout the literature.

Conclusion Endometrial cancer risk may be influenced by SNPs in genes involved in cell survival, oestrogen metabolism and transcriptional control. Larger cohorts are needed to identify more variants with genome-wide significance.

  • endometrial cancer
  • single nucleotide polymorphism (SNP)
  • systematic review
  • genetic epidemiology
  • risk prediction

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  • Contributors CB planned the study, did the systematic review, analysed the data and wrote the manuscript. DJT and AL supervised the study and provided statistical support for the analysis. MJS supervised the study. NAJR and AN supported data acquisition. DGE and EJC designed and planned the study, provided supervision and wrote the manuscript. EJC provided funding for the study. All authors reviewed and approved the final manuscript.

  • Funding CB, DGE, AL, MJS and EJC are all supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (IS-BRC-1215-20007). NAJR was supported through a Medical Research Council (MRC) Doctoral Research Fellowship (MR/M018431/1), EJC through an NIHR Clinician Scientist Fellowship (NIHR-CS-012-009) and DGE is an NIHR Senior Investigator (NF-SI-0513–10076). This research was funded by the NIHR Manchester BRC.

  • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The protocol for this systematic review was published at PROSPERO and the data that inform this manuscript are available upon reasonable request from the corresponding author.

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