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Risk Factors for Endometrial Cancer: a Review of the Evidence Risk factors for endometrial cancer: A review of the evidence 2019 Risk factors for endometrial cancer: A review of the evidence was prepared and produced by: Cancer Australia Locked Bag 3 Strawberry Hills NSW 2012 Australia Tel: +61 2 9357 9400 Fax: +61 2 9357 9477 canceraustralia.gov.au © Cancer Australia 2019. ISBN Online: 978–1–74127–342–7 Recommended citation Cancer Australia, 2019. Risk factors for endometrial cancer: A review of the evidence, Cancer Australia, Surry Hills, NSW. Risk factors for endometrial cancer: A review of the evidence can be downloaded from the Cancer Australia website: canceraustralia.gov.au Copyright statements Internet sites This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from Cancer Australia to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Publications and Copyright contact officer, Cancer Australia, Locked Bag 3, Strawberry Hills, NSW 2012. Disclaimer Cancer Australia does not accept any liability for any injury, loss or damage incurred by use of or reliance on the information. Cancer Australia develops material based on the best available evidence, however it cannot guarantee and assumes no legal liability or responsibility for the currency or completeness of the information. Endometrial cancer risk factors: A review of the evidence i Table of contents 1 Introduction............................................................................................................................... 6 1.1 Context ..............................................................................................................................6 1.2 Endometrial cancer aetiology ......................................................................................7 1.2.1 Classification and histopathology .................................................................7 1.2.2 Pathogenesis and genetics ............................................................................8 1.3 Approach ..........................................................................................................................9 2 Methods .................................................................................................................................. 10 2.1 Overview......................................................................................................................... 10 2.2 Search strategy ............................................................................................................. 10 2.3 Study selection .............................................................................................................. 12 2.4 Data extraction and synthesis .................................................................................... 13 2.4.1 Assessment of evidence base ..................................................................... 13 2.4.2 Selection of best estimate of risk ................................................................. 16 3 Endometrial cancer risk factors ........................................................................................... 17 3.1 General factors ............................................................................................................. 17 3.1.1 Age ................................................................................................................... 17 3.2 Family history & genetics ............................................................................................. 19 3.2.1 Family history of endometrial cancer or colorectal cancer ................. 19 3.2.2 Mismatch repair gene mutations ............................................................... 21 3.2.3 PTEN gene mutation ...................................................................................... 24 3.3 Endogenous hormones ................................................................................................ 26 3.3.1 Age at menarche .......................................................................................... 26 3.3.2 Age at menopause ....................................................................................... 27 3.3.3 Breastfeeding ................................................................................................. 28 3.3.4 Parity ................................................................................................................. 30 3.3.5 Polycystic ovary syndrome (PCOS) ............................................................ 31 3.4 Exogenous Hormones................................................................................................... 33 3.4.1 Hormonal contraceptionoral contraceptives ...................................... 33 3.4.2 Hormonal infertility treatment ...................................................................... 35 3.4.3 Intrauterine device (IUD) contraception................................................... 36 3.4.4 Menopausal hormone therapy/Hormone replacement therapy............................................................................................................. 38 3.5 Lifestyle factors .............................................................................................................. 42 3.5.1 Alcohol consumption .................................................................................... 42 3.5.2 Body fatness .................................................................................................... 44 3.5.3 Coffee and tea .............................................................................................. 47 3.5.4 Dietacrylamide ........................................................................................... 51 3.5.5 Dietfat ........................................................................................................... 52 3.5.6 Dietglycaemic load ................................................................................... 53 3.5.7 Environmental tobacco smoke ................................................................... 55 Endometrial cancer risk factors: A review of the evidence ii 3.5.8 Physical activity .............................................................................................. 56 3.5.9 Sedentary behaviour .................................................................................... 58 3.5.10 Tobacco smoking .......................................................................................... 60 3.5.11 Weight loss ....................................................................................................... 62 3.6 Medical factors ............................................................................................................. 64 3.6.1 Non–steroidal anti–inflammatory drugs (NSAIDs) .................................... 64 3.6.2 Diabetes........................................................................................................... 65 3.6.3 Endometrial hyperplasia and polyps ......................................................... 67 3.6.4 Endometriosis .................................................................................................. 71 3.6.5 Gall bladder disease ..................................................................................... 72 3.6.6 Hypertension ................................................................................................... 73 3.6.7 Metformin ........................................................................................................ 74 3.6.8 Oral bisphosphonates ................................................................................... 75 3.6.9 Paracetamol (acetaminophen) ................................................................. 76 3.6.10 Selective oestrogen receptor modifiers .................................................... 77 3.6.11 Statins ............................................................................................................... 82 3.6.12 Stress ................................................................................................................. 83 Appendix A Acknowledgements .................................................................................................... 85 Appendix B IARC and WCRF/AICR classifications ........................................................................ 86 Appendix C IARC and WCRF/AICR categories of evidence and criteria for grading carcinogenicity ...................................................................................................................... 88 Glossaries ....................................................................................................................................... 92 Abbreviations ...................................................................................................................................... 97 References ....................................................................................................................................
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