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Cancer Causes & Control
Published in: Cancer Causes & Control 2/2020

01-02-2020 | Endometrial Cancer | Original Paper

Case–control study of endogenous sex steroid hormones and risk of endometrial cancer

Authors: Christine M. Friedenreich, Jeroen W. G. Derksen, Thomas Speidel, Darren R. Brenner, Emily Heer, Kerry S. Courneya, Linda S. Cook

Published in: Cancer Causes & Control | Issue 2/2020

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Abstract

Background

Epidemiologic evidence regarding the role of endogenous sex hormones in endometrial cancer etiology remains inconsistent. The objective of this study was to investigate if circulating levels of endogenous estrone, estradiol, sex hormone binding globulin (SHBG), testosterone, and androstenedione are associated with endometrial cancer risk.

Methods

We conducted a population-based case–control study of 522 incident endometrial cancer cases and 976 population controls, in Alberta, Canada from 2002 to 2006. Study participants completed in-person interviews and provided fasting blood samples. Sex hormone levels were determined by enzyme-linked immunosorbent assays.

Results

Higher levels of androstenedione were associated with increased endometrial cancer risk (OR 1.44, 95% CI 1.04–2.02). Endometrial cancer risk in pre- and peri-menopausal women was reduced for the highest versus lowest quartiles of estrone (OR 0.44, 95% CI 0.22–0.88) and estradiol (OR 0.30, 95% CI 0.14–0.65), but in post-menopausal women, the endometrial cancer risk was increased for the highest versus lowest quartile of androstenedione (OR 1.82, 95% CI 1.25–2.65). In addition, endometrial cancer risk in normal/underweight women was decreased for the highest versus lowest quartile of serum SHBG (OR 0.39, 95% CI 0.19–0.84).

Conclusions

Overall, positive associations were found for androstenedione concentrations, while sub-group analyses revealed = inverse associations with estrogens and SHBG. Results of this study provide empirical evidence for the role of circulating sex hormones in endometrial cancer etiology and highlight the importance of modifiable factors that contribute to changes in sex hormone concentration levels.
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424CrossRefPubMed
2.
3.
Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I (2005) Endometrial cancer. Lancet 366:491–505CrossRefPubMed
4.
Siiteri PK (1978) Steroid hormones and endometrial cancer. Cancer Res 38:4360–4366PubMed
5.
Key T, Pike M (1988) The dose-effect relationship between'unopposed'oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer 57:205CrossRefPubMedPubMedCentral
6.
Pauklin S, Sernandez IV, Bachmann G, Ramiro AR, Petersen-Mahrt SK (2009) Estrogen directly activates AID transcription and function. J Exp Med 206:99–111CrossRefPubMedPubMedCentral
7.
Brown SB, Hankinson SE (2015) Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Steroids 99:8–10CrossRefPubMed
8.
Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569–578CrossRefPubMed
9.
Brenner DR (2014) Cancer incidence due to excess body weight and leisure-time physical inactivity in Canada: Implications for prevention. Prev Med 66:131–139CrossRefPubMed
10.
11.
Lu L, Lee S, Mayne S et al (2012) Synergistic interplay between long-term overweight and long menstrual years in endometrial cancer. Cancer Res 72:633–633
12.
Kaaks R, Lukanova A, Kurzer MS (2002) Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomark Prev 11:1531–1543
13.
Jamison PM, Noone AM, Ries LA, Lee NC, Edwards BK (2013) Trends in endometrial cancer incidence by race and histology with a correction for the prevalence of hysterectomy, SEER 1992 to 2008. Cancer Epidemiol Biomark Prev 22:233–241CrossRef
14.
Dossus L, Allen N, Kaaks R et al (2010) Reproductive risk factors and endometrial cancer: the European prospective investigation into Cancer and Nutr. Int J Cancer 127:442–451PubMed
15.
Aune D, Navarro Rosenblatt DA, Chan DS et al (2015) Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Ann Oncol 26:1635–1648CrossRefPubMed
16.
Voskuil DW, Monninkhof EM, Elias SG et al (2007) Physical activity and endometrial cancer risk, a systematic review of current evidence. Cancer Epidemiol Biomark Prev 16:639–648CrossRef
17.
Keum N, Ju W, Lee DH et al (2014) Leisure-time physical activity and endometrial cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer 135:682–694CrossRefPubMed
18.
Friedenreich CM, Cook LS, Magliocco AM, Duggan MA, Courneya KS (2010) Case-control study of lifetime total physical activity and endometrial cancer risk. Cancer Causes Control 21:1105–1116CrossRefPubMedPubMedCentral
19.
Friedenreich CM, Biel RK, Lau DC et al (2011) Case-control study of the metabolic syndrome and metabolic risk factors for endometrial cancer. Cancer Epidemiol Prev Biomark 20:2384–2395CrossRef
20.
Friedenreich CM, Langley AR, Speidel TP et al (2012) Case-control study of markers of insulin resistance and endometrial cancer risk. Endocr Relat Cancer 19:785–792CrossRefPubMedPubMedCentral
21.
Friedenreich CM, Speidel TP, Neilson HK et al (2013) Case-control study of lifetime alcohol consumption and endometrial cancer risk. Cancer Causes Control 24:1995–2003CrossRefPubMedPubMedCentral
22.
Aleem FA, Moukhtar MA, Hung HC, Romney SL (1976) Plasma estrogen in patients with endometrial hyperplasia and carcinoma. Cancer 38:2101–2104CrossRefPubMed
23.
Allen NE, Key TJ, Dossus L et al (2008) Endogenous sex hormones and endometrial cancer risk in women in the European prospective investigation into cancer and nutrition (EPIC). Endocr Relat Cancer 15:485–497CrossRefPubMedPubMedCentral
24.
Austin H, Austin JM Jr, Partridge EE, Hatch KD, Shingleton HM (1991) Endometrial cancer, obesity, and body fat distribution. Cancer Res 51:568–572PubMed
25.
Benjamin F, Deutsch S (1976) Plasma levels of fractionated estrogens and pituitary hormones in endometrial carcinoma. Am J Obstet Gynecol 126:638–647CrossRefPubMed
26.
Bremond AG, Claustrat B, Rudigoz R, Seffert P, Corniau J (1982) Estradiol, androstenedione, testosterone, and dehydroepiandrosterone sulfate in the ovarian and peripheral blood of postmenopausal patients with and without endometrial cancer. Gynecol Oncol 14:119–124CrossRefPubMed
27.
Carlstrom K, Damber MG, Furuhjelm M, Joelsson I, Lunell NO, von Schoultz B (1979) Serum levels of total dehydroepiandrosterone and total estrone in postmenopausal women with special regard to carcinoma of the uterine corpus. Acta Obstet Gynecol Scand 58:179–181CrossRefPubMed
28.
Gimes G, Szarvas Z, Siklosi G (1986) Endocrine factors in the etiology of endometrial carcinoma. Neoplasma 33:393–397PubMed
29.
Judd HL, Lucas WE, Yen SS (1976) Serum 17β-estradiol and estrone levels in postmenopausal women with and without endometrial cancer. J Clin Endocrinol Metab 43:272–278CrossRefPubMed
30.
Lukanova A, Lundin E, Micheli A et al (2004) Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 108:425–432CrossRefPubMed
31.
Möllerström G, Carlström K, Lagrelius A, Einhorn N (1993) Is there an altered steroid profile in patients with endometrial carcinoma? Cancer 72:173–181CrossRefPubMed
32.
Nagamani M, Hannigan EV, Dillard JREA, Dinh TV (1986) Ovarian Steroid Secretion in Postmenopausal Women with and without Endometrial Cancer. J Clin Endocr Metab 62:508–512CrossRefPubMed
33.
Nisker J, Hammond G, Davidson B et al (1980) Serum sex hormone-binding globulin capacity and the percentage of free estradiol in postmenopausal women with and without endometrial carcinoma. A new biochemical basis for the association between obesity and endometrial carcinoma. Am J Obstet Gynecol 138:637CrossRefPubMed
34.
Nyholm HC, Nielsen AL, Lyndrup J, Dreisler A, Hagen C, Haug E (1993) Plasma oestrogens in postmenopausal women with endometrial cancer. Br J Obstet Gynaecol 100:1115–1119CrossRefPubMed
35.
Oettinger M, Samberg I, Levitan Z, Eibschitz I, Sharf M (1984) Hormonal profile of endometrial cancer. Gynecol Obstet Invest 17:225–235CrossRefPubMed
36.
Pettersson B, Bergstrom R, Johansson ED (1986) Serum estrogens and androgens in women with endometrial carcinoma. Gynecol Oncol 25:223–233CrossRefPubMed
37.
Potischman N, Hoover RN, Brinton LA et al (1996) Case—control study of endogenous steroid hormones and endometrial cancer. J Nat Cancer Ins 88:1127–1135CrossRef
38.
Von Holst T, Klinga K, Runnebaum B (1981) Hormone levels in healthy post-menopausal women and in women with post-menopausal bleeding with or without endometrial carcinoma. Maturitas 3:315–320CrossRef
39.
Zeleniuch-Jacquotte A, Akhmedkhanov A, Kato I et al (2001) Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study. Br J Cancer 84:975–981CrossRefPubMedPubMedCentral
40.
Jasonni VM, Bulletti C, Franceschetti F et al (1984) Estrone sulphate plasma levels in postmenopausal women with and without endometrial cancer. Cancer 53:2698–2700CrossRefPubMed
41.
Falsetti L, Omodei U, Dordoni D et al (1982) Profiles and endocrine correlations in endometrial carcinoma. Eur J Gynaecol Oncol 4:30–34
42.
Scirpa P, Mango D, Battaglia F, Scirpa S, Montemurro A (1982) Plasma androstenedione and oestrone levels before and after the menopause. I. Glandular hyperplasia and adenocarcinoma of the endometrium. Maturitas 4:33–42CrossRefPubMed
43.
Judd H, Davidson B, Frumar A, Shamonki I, Lagasse L, Ballon S (1980) Serum androgens and estrogens in postmenopausal women with and without endometrial cancer. Am J Obs Gynecol 136:859–871CrossRef
44.
Davidson B, Gambone J, Lagasse L et al (1981) Free estradiol in postmenopausal women with and without endometrial cancer. J Clin Endocrinol Metab 52:404–407CrossRefPubMed
45.
Bonney R, Scanlon M, Jones D, Reed M, Anderson M, James V (1986) The relationship between oestradiol metabolism and adrenal steroids in the endometrium of postmenopausal women with and without endometrial cancer. Eur J Cancer Clin Oncol 22:953–961CrossRefPubMed
46.
Cleveland WS, Devlin SJ (1988) Locally weighted regression: an approach to regression analysis by local fitting. J Am Stat Assoc 83:596–610CrossRef
47.
Sarle W (1990) The VARCLUS Procedure. In: Institute SAS (ed) SAS/STAT User’s Guide. SAS Institute, Cary, pp 1641–1659
48.
Hosmer DW, Hosmer T, Le Cessie S, Lemeshow S (1997) A comparison of goodness-of-fit tests for the logistic regression model. Stat Med 16:965–980CrossRefPubMed
49.
Clendenen TV, Hertzmark K, Koenig KL et al (2016) Premenopausal circulating androgens and risk of endometrial cancer: results of a prospective study. Horm Cancer 7:178–187CrossRefPubMedPubMedCentral
50.
Audet-Walsh E, Lepine J, Gregoire J et al (2011) Profiling of endogenous estrogens, their precursors, and metabolites in endometrial cancer patients: association with risk and relationship to clinical characteristics. J Clin Endocrinol Metab 96:E330–E339CrossRefPubMed
51.
Hoffman B, Schorge J, Bradshaw K, Halvorson L, Schaffer J, Corton M (2012) Williams gynecology: endometrial cancer, 2nd edn. McGraw-Hill, New York
52.
Shao Y, Cheng S, Hou J et al (2016) Insulin is an important risk factor of endometrial cancer among premenopausal women: a case-control study in China. Tumour Biol 37:4721–4726CrossRefPubMed
53.
Lambrinoudaki I, Armeni E, Rizos D et al (2011) Sex hormones in postmenopausal women receiving low-dose hormone therapy: the effect of BMI. Obesity (Silver Spring) 19:988–993CrossRef
54.
Mollerstrom G, Carlstrom K, Lagrelius A, Einhorn N (1993) Is there an altered steroid profile in patients with endometrial carcinoma? Cancer 72:173–181CrossRefPubMed
55.
Brinton LA, Trabert B, Anderson GL et al (2016) Serum Estrogens and Estrogen Metabolites and Endometrial Cancer Risk among Postmenopausal Women. Cancer Epidemiol Biomark Prev 25:1081–1089CrossRef
56.
Burleigh A, Talhouk A, Gilks CB, McAlpine JN (2015) Clinical and pathological characterization of endometrial cancer in young women: identification of a cohort without classical risk factors. Gynecol Oncol 138:141–146CrossRefPubMed
57.
Garg K, Soslow RA (2014) Endometrial carcinoma in women aged 40 years and younger. Arch Pathol Lab Med 138:335–342CrossRefPubMed
58.
Gunter MJ, Hoover DR, Yu H et al (2008) A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomark Prev 17:921–929CrossRef
59.
Kim C, Harlow SD, Zheng H, McConnell DS, Randolph JF Jr (2017) Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition. Womens Midlife Health 3:9CrossRefPubMedPubMedCentral
60.
Michels KA, Brinton LA, Wentzensen N et al (2019) Postmenopausal androgen metabolism and endometrial cancer risk in the Women's Health Initiative Observational Study. JNCI Cancer Spectr 3:029CrossRef
61.
Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, von Muhlen D (2000) Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study. J Clin Endocrinol Metab 85:645–651PubMed
62.
Hankinson SE, Manson JE, Spiegelman D, Willett WC, Longcope C, Speizer FE (1995) Reproducibility of plasma hormone levels in postmenopausal women over a 2-3-year period. Cancer Epidemiol Biomark Prev 4:649–654
63.
Cook LS, Dong Y, Round P, Huang X, Magliocco AM, Friedenreich CM (2014) Hormone contraception before the first birth and endometrial cancer risk. Cancer Epidemiol Biomark Prev 23:356–361CrossRef
64.
Maxwell GL, Schildkraut JM, Calingaert B et al (2006) Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk. Gynecol Oncol 103:535–540CrossRefPubMed
65.
Cook LS, Doherty J, Weiss NS, Chen C (2003) Endometrial cancer epidemiology and molecular endocrinology. In: Henderson BE, Ponder B, Ross RK (eds) Hormones genes and cancer. Oxford University Press, New York
66.
Collaborative Group on Epidemiological Studies on Endometrial Cancer (2015) Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol 16:1061–1070CrossRef
Metadata
Title
Case–control study of endogenous sex steroid hormones and risk of endometrial cancer
Authors
Christine M. Friedenreich
Jeroen W. G. Derksen
Thomas Speidel
Darren R. Brenner
Emily Heer
Kerry S. Courneya
Linda S. Cook
Publication date
01-02-2020
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 2/2020
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-019-01260-5

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