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. 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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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