Uterine cancer risk

Preventable cases

Uterine cancer cases are preventable, UK, 2015

 

Caused by obesity

Uterine cancer cases caused by overweight and obesity, UK, 2015

 

The estimated lifetime risk of being diagnosed with uterine cancer is 1 in 36 (3%) for females born after 1960 in the UK.[1]

These figures have been calculated on the assumption that the possibility of having more than one diagnosis of uterine cancer over the course of a lifetime is very low (‘Current Probability’ method).[2

References

  1. Lifetime risk estimates calculated by the Statistical Information Team at Cancer Research UK. Based on Office for National Statistics (ONS) 2016-based Life expectancies and population projections. Accessed December 2017, and Smittenaar CR, Petersen KA, Stewart K, Moitt N. Cancer Incidence and Mortality Projections in the UK Until 2035. Brit J Cancer 2016. 
  2. Esteve J, Benhamou E and Raymond L. Descriptive epidemiology. IARC Scientific Publications No.128, Lyon, International Agency for Research on Cancer, pp 67-68 1994. 

About this data

Data is for UK, past and projected cancer incidence and mortality and all-cause mortality rates for those born in 1961, ICD-10 C54-C55.

The calculations used past and projected cancer incidence and mortality and all-cause mortality rates for those born in 1961 to project risk over the lifetime of those born in 1961 (cohort method).[1] Projections are based on observed incidence and mortality rates and therefore implicitly include changes in cancer risk factors, diagnosis and treatment.

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34% of uterine cancer cases in the UK are preventable.[1]

Uterine cancer is associated with a number of risk factors.[2-4]

Uterine Cancer Risk Factors

  Increases risk Decreases risk
'Sufficient' or 'convincing' evidence
  • Hormone replacement therapy (HRT) (oestrogen-progestogen and oestrogen-only)
  • Tamoxifen
  • Body fatness
  • Oestrogen-progestogen contraceptives
'Limited' or 'probable' evidence
  • Diethylstilbestrol
  • Glycaemic load
  • Physical activity
  • Coffee

International Agency for Research on Cancer (IARC) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classifications.

All classifications are for endometrium

See also

Want to generate bespoke preventable cancers stats statements? Download our interactive statement generator.

Find out more about the definitions and evidence for this data

Learn how attributable risk is calculated

References

  1. Brown KF, Rumgay H, Dunlop C, et al. The fraction of cancer attributable to known risk factors in England, Wales, Scotland, Northern Ireland, and the UK overall in 2015. British Journal of Cancer 2018.
  2. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 122*. Accessed October 2018.
  3. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug 25;375(8):794-8.
  4. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed October 2018.
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The majority of endometrial cancers are oestrogen Open a glossary item-driven.[1,2] Oestrogen and progesterone Open a glossary item work in balance to regulate the female reproductive system, with oestrogen stimulating endometrial cell growth. But oestrogen unopposed by progesterone (e.g. after menopause, or during use of oestrogen-only hormone replacement therapy) increases endometrial cancer risk. Endometrial cancer Open a glossary item risk is 2.1-2.7 times higher in women with the highest circulating oestrogen levels, a cohort study showed.[3]

Many factors associated with uterine cancer risk are causes or markers of higher/lower oestrogen exposure, e.g. hormone replacement therapy (HRT) Open a glossary item, higher parity and longer menstrual lifespan are linked with higher oestrogen exposure, and use of oral contraceptives is linked with lower exposure. This is probably their mechanism of association with uterine cancer risk.

Irregular, infrequent, absent or anovulatory menstrual cycles may reflect exposure to oestrogen unopposed by progesterone, and so may be associated with increased uterine cancer risk.[4]

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International Agency for Research on Cancer (IARC) classifies the role of this risk factor in cancer development.[1]

Oestrogen-only HRT

Endometrial cancer Open a glossary item risk is 2.3 times higher in oestrogen-only hormone replacement therapy (HRT) Open a glossary item ever-users versus non users, a meta-analysis showed.[2] Studies with endometrial cancer as the endpoint are now rare, because the risks of oestrogen-only HRT users are now well-known, so users are closely monitored and their treatment stopped or changed if endometrial hyperplasia develops.[3]

Endometrial hyperplasia risk is not associated with use of low-dose oestrogen-only HRT for a year, a meta-analysis of randomised controlled trials (RCT) Open a glossary item showed.[4] At moderate and high doses, and at low-dose but 18-24 months use, endometrial hyperplasia risk is markedly higher in oestrogen-only HRT users versus placebo users.[4]

Endometrial cancer risk increases with duration of oestrogen-only HRT use.[3] Endometrial cancer risk decreases after cessation of oestrogen-only HRT use, though risk is still higher in ex-users than never users some years after cessation.[2,5] Endometrial cancer risk may only be associated with oestrogen-only HRT use in healthy-weight women, perhaps because endogenous oestrogen levels are already so high in women with excess body weight, that exogenous oestrogen has limited additional impact.[6,7]

Oestrogen-progestogen HRT

Endometrial cancer Open a glossary item risk is 22% lower in ever-users of continuous combined HRT (oestrogen and progesterone taken together daily), versus non-users, a meta-analysis of observational studies showed.[7]

Endometrial hyperplasia and endometrial cancer risk is not associated with use of continuous combined HRT, a meta-analysis of Randomised Controlled Trials (RCTs) showed.[4]

The association between endometrial cancer and cyclic/sequential combined HRT (oestrogen taken daily with progesterone added for part of the menstrual cycle) varies with the proportion of the cycle where progesterone is used. Endometrial cancer risk is not associated with ever-use of cyclic/sequential combined HRT with 10-24 days progesterone per month, a meta-analysis of observational studies showed; but is 76% higher in ever-users of cyclic/sequential combined HRT with less than 10 days of progesterone per month, versus non-users.[7]

Endometrial hyperplasia risk is not associated with use of combined sequential/cyclic HRT overall, a meta-analysis of RCTs showed.[7]

Endometrial cancer risk is 1.79-3.56 times higher in ever users of tibolone (synthetic oestrogen) versus non-users, a systematic review showed.[5]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 122. Accessed October 2018.
  2. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis 1995 Feb;85(2):304-13.
  3. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. 2012 Jul 11;7:CD004143.
  4. Furness S, Roberts H, Marjoribanks J, Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. 2012 Aug 15;8:CD000402.
  5. Sjögren LL, Mørch LS, Løkkegaard E. Hormone replacement therapy and the risk of endometrial cancer: A systematic review. Maturitas. 2016 Sep;91:25-35.
  6. Beral V, Bull D, Reeves G. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet, 2005. 365(9470): 1543-51.
  7. Brinton LA, Felix AS. Menopausal hormone therapy and risk of endometrial cancer. J Steroid Biochem Mol Biol. 2014 Jul;142:83-9.
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Having children

Endometrial cancer Open a glossary item risk is 35-42% higher in nulliparous women (those who have had no children), compared with parous women (those who have had children), a cohort study and pooled analysis showed.[1,2] Endometrial cancer risk decreases with greater number of full-term pregnancies.[2]

Increased progesterone levels during pregnancy and physical changes to the uterus during and after childbirth may explain the link between parity and endometrial cancer risk.[1,2]

Younger age at first giving birth

Endometrial cancer risk is 44% higher in women who were aged 25 or younger when they gave birth to their last child, compared with women who did so aged 40+, a pooled analysis showed.[3]

Younger age at menarche

Endometrial cancer Open a glossary item risk among parous women is 11% higher in those aged under 13 at menarche (first menstrual period), compared with those aged 13+ at menarche, a pooled analysis showed.[1] Endometrial cancer risk among nulliparous women is not associated with age at menarche.[1]

Older age at menopause

Endometrial cancer risk among parous women is 22% higher in those aged 50-54 at menopause, compared with those aged under 45 at menopause, a pooled analysis showed.[1] Endometrial cancer risk among nulliparous women is 34% higher in those aged 50-54 at menopause, compared with those aged under 45 at menopause.[1]

Longer menstrual lifespan results in greater cumulative oestrogen exposure, which may explain the link between parity and endometrial cancer risk.[2]

References

  1. Schonfield SJ, Hartge P, Pfeiffer RM et al. An aggregated analysis of hormonal factors and endometrial cancer risk by parity. Cancer. 2013 Apr 1;119(7):1393-401.
  2. Dossus L, Allen N, Kaaks R et al. Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2010 Jul 15;127(2):442-51.
  3. Setiawan VW, Pike MC, Karageorgi S et al. Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium. Am J Epidemiol. 2012 Aug 15;176(4):269-78. Epub 2012 Jul 23.
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International Agency for Research on Cancer (IARC) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classify the role of this risk factor in cancer development.[1,2] 34% of uterine cancer cases in the UK are caused by overweight and obesity.[3]

Endometrial cancer risk is 34% higher in overweight (body mass index [BMI] 25-30) women, and 2.5 times higher in obese (BMI 30+) women, both compared with healthy-weight (BMI less than 25) women, a meta-analysis showed.[4] The association may be stronger in women who have never used Hormone replacement therapy (HRT).[5]

Endometrial cancer risk is 81% higher per 5-unit BMI gained during adulthood, a meta-analysis showed.[6]

Greater body fatness is associated with higher sex hormone levels (fatty tissue produces more oestrogen) and higher leptin levels, which may partly explain the link between body fatness and endometrial cancer risk.[2,7,8]

Endometrial cancer risk is 2.2 times higher in women with the highest waist circumference versus those with the lowest, a meta-analysis showed.[8]

UK portrait version shown here. Country versions, cancers caused by other risk factors, and landscape formats are available for free from our cancer risk publications.

References

  1. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug 25;375(8):794-8.
  2. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed May 2017.
  3. Brown KF, Rumgay H, Dunlop C, et al. The fraction of cancer attributable to known risk factors in England, Wales, Scotland, Northern Ireland, and the UK overall in 2015. British Journal of Cancer 2018.
  4. Jenabi E, Poorolajal J. The effect of body mass index on endometrial cancer: a meta-analysis. Public Health. 2015 Jul;129(7):872-80.
  5. Crosbie EJ, Zwahlen M, Kitchener HC, et al. Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3119-30.
  6. Stevens VL, Jacobs EJ, Patel AV, et al. Body weight in early adulthood, adult weight gain, and risk of endometrial cancer in women not using postmenopausal hormones. Cancer Causes Control. 2014 Mar;25(3):321-8.
  7. Wang PP, He XY, Wang R, et al. High leptin level is an independent risk factor of endometrial cancer: a meta-analysis. Cell Physiol Biochem 2014;34(5):1477-84.
  8. Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Giugliano D. Metabolic syndrome and endometrial cancer: a meta-analysis. Endocrine. 2014 Feb;45(1):28-36.
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Polycystic ovary syndrome (PCOS)

Endometrial cancer risk is 2.8 times higher in women with polycystic ovary syndrome (PCOS) versus those without the condition, a meta-analysis showed.[1] Endometrial cancer risk is 4.1 times higher in women aged 54 and under (e.g. premenopausal), versus women of a similar age without PCOS.[1]

Increased endometrial cancer risk in PCOS probably reflects exposure to unopposed oestrogen. PCOS often coexists with metabolic syndrome so insulin pathways may also be implicated.[2]

Endometrial polyps

Among women with endometrial polyps, endometrial cancer occurs in 2-5% of cases, a meta-analysis showed.[3] Endometrial polyps are more likely to be malignant in postmenopausal than in premenopausal women.[3]

Diabetes

Endometrial cancer Open a glossary item risk is 40-81% higher in diabetics compared with non-diabetics, meta-analyses have shown,[4,5] however overweight/obesity in diabetics may largely explain this association.[6] Endometrial/uterine cancer risk among diabetics does not vary with diabetes treatment.[7,8]

References

  1. Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2014 Sep-Oct;20(5):748-58.
  2. Palomba S, Falbo A, Zullo F, Orio F Jr. Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev. 2009 Feb;30(1):1-50.
  3. Lee SC, Kaunitz AM, Sanchez-Ramos L, Rhatigan RM. The oncogenic potential of endometrial polyps: a systematic review and meta-analysis. Obstet Gynecol. 2010 Nov;116(5):1197-205.
  4. Luo J, Beresford S, Chen C, et al. Association between diabetes, diabetes treatment and risk of developing endometrial cancer. Br J Cancer 2014 Sep;111(7):1432-9.
  5. Becker C, Jick SS, Meier CR, et al. Metformin and the risk of endometrial cancer: a case-control analysis. Gynecol Oncol. 2013 Jun;129(3):565-9.
  6. Ferrara A, Lewis JD, Quesenberry CP Jr, et al. Cohort study of pioglitazone and cancer incidence in patients with diabetes. Diabetes Care. 2011 Apr;34(4):923-9.
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World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classifies the role of this risk factor as probably protective against endometrial cancer.[1]

Endometrial cancer risk is 15-27% lower in the most physically active (recreational) women versus the least, meta-analyses have shown.[2-4] Endometrial cancer risk is 5% lower per 1 hour/week increment in leisure-time physical activity,[4] and 32% lower in women who spend the least time sitting versus those who spend the most.[5] Endometrial cancer risk is not associated with household physical activity, a meta-analysis showed. [6]

References

  1. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Findings & Reports. Accessed October 2018.
  2. Voskuil DW, Monninkhof EM, Elias SG, et al. Physical activity and endometrial cancer risk, a systematic review of current evidence. Cancer Epidemiol Biomarkers Prev 2007; 16(4): 639-48.
  3. Moore SC, Gierach GL, Schatzkin A, et al. Physical activity, sedentary behaviours, and the prevention of endometrial cancer. Br J Cancer. 2010 Sep 28;103(7):933-8.
  4. Keum N, Ju W, Lee DH, et al. Leisure-time physical activity and endometrial cancer risk: Dose-response meta-analysis of epidemiological studies. Int J Cancer. 2013 Dec 20.
  5. Schmid D, Leitzmann MF. Television viewing and time spent sedentary in relation to cancer risk: a meta-analysis. J Natl Cancer Inst. 2014 Jun 16;106(7). pii: dju098.
  6. Shi Y, Li T, Wang Y, et al. Household physical activity and cancer risk: a systematic review and dose-response meta-analysis of epidemiological studies. Sci Rep. 2015;5:14901
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Oral contraceptives (OCs)

International Agency for Research on Cancer (IARC) classifies the role of this risk factor as protective against endometrial cancer Open a glossary item.[1] 25% of uterine cancer cases in the UK are prevented by OC use.[2]

Endometrial cancer risk is 26-43% lower in OC ever- versus never-users, meta-analyses have shown.[3,4] The lower risk may be limited to women with 5+ years OC use,[3] and may persist for 20 years after OC cessation.[5]

Intrauterine device (IUD)

Endometrial cancer risk is 19% lower in ever-users of IUDs compared with never-users, a pooled analysis showed.[6]

References

  1. International Agency for Research on Cancer. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 122. Accessed October 2018.
  2. Calculated by the Statistical Information Team at Cancer Research UK, 2018. Based on Brown KF, Rumgay H, Dunlop C, et al. The fraction of cancer attributable to known risk factors in England, Wales, Scotland, Northern Ireland, and the UK overall in 2015. British Journal of Cancer 2018. 
  3. Havrilesky LJ, Gierisch JM, Moorman PG, et al. Oral contraceptive use for the primary prevention of ovarian cancer. Evid Rep Technol Assess (Full Rep). 2013 Jun;(212):1-514.
  4. Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol. 2013 Jul 10;31(20):2607-18.
  5. Mueck AO, Seeger H, Rabe T. Hormonal contraception and risk of endometrial cancer: a systematic review. Endocr Relat Cancer. 2010 Sep 23;17(4):R263-71.
  6. Felix AS, Gaudet MM, La Vecchia C, et al. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium. Int J Cancer. 2015 Mar 1; 136(5): E410–E422.
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World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) classifies the role of this risk factor as probably protective against endometrial cancer.[1]

Endometrial cancer risk is 21% lower in women who have the highest intake of coffee, compared with those with the lowest intake, a meta-analysis showed.[2]

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