Abstract
Purpose
Obesity is a public health epidemic and a major risk factor for endometrial cancer. Here, we identify key aspects of body size which jointly, over the life-course (since adolescence), are associated with endometrial cancer risk.
Methods
Among 88,142 participants in the California Teachers Study, 887 were diagnosed with invasive type 1 endometrial cancer between 1997–1998 and 2012. Multivariable Cox proportional hazards models provided estimates of hazard rate ratios (HR) and 95% confidence intervals (CI) for endometrial cancer associated with life-course body size phenotypes, which incorporated validated measures.
Results
Among women currently using hormone therapy, endometrial cancer risk was only associated with height (HR 1.78, 95% CI 1.32–2.40 for ≥67 vs. <67 inches). Among women not using hormone therapy, tall women who were overweight/obese in adolescence (HR 4.33, 95% CI 2.51–7.46) or who became overweight/obese as adults (HR 4.74, 95% CI 2.70–8.32) were at greatest risk.
Conclusions
Considering absolute body mass, changes in adiposity over time, and body fat distribution together, instead of each measure alone, we identified lifetime obesity phenotypes associated with endometrial cancer risk. These results more clearly define specific risk groups, and may explain inconsistent findings across studies, improve risk prediction models, and aid in developing targeted interventions for endometrial cancer.
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References
World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: global perspective. AICR, Washington
World Cancer Research Fund/American Institute for Cancer Research (2013) Continuous update project report. Food, nutrition, physical activity, and the prevention of endometrial cancer. AICR, Washington, DC
Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM, van den Brandt PA, van de Vijver K, Thompson PJ, Strom BL, Spurdle AB, Soslow RA, Shu XO, Schairer C, Sacerdote C, Rohan TE, Robien K, Risch HA, Ricceri F, Rebbeck TR, Rastogi R, Prescott J, Polidoro S, Park Y, Olson SH, Moysich KB, Miller AB, McCullough ML, Matsuno RK, Magliocco AM, Lurie G, Lu L, Lissowska J, Liang X, Lacey JV Jr, Kolonel LN, Henderson BE, Hankinson SE, Hakansson N, Goodman MT, Gaudet MM, Garcia-Closas M, Friedenreich CM, Freudenheim JL, Doherty J, De Vivo I, Courneya KS, Cook LS, Chen C, Cerhan JR, Cai H, Brinton LA, Bernstein L, Anderson KE, Anton-Culver H, Schouten LJ, Horn-Ross PL (2013) Type I and II endometrial cancers: have they different risk factors? J Clin Oncol 31(20):2607–2618. doi:10.1200/jco.2012.48.2596
Keum N, Greenwood DC, Lee DH, Kim R, Aune D, Ju W, Hu FB, Giovannucci EL (2015) Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies. J Natl Cancer Inst 107(2):1–14. doi:10.1093/jnci/djv088
Renehan AG, MacKintosh ML, Crosbie EJ (2016) Obesity and endometrial cancer: unanswered epidemiological questions. Br J Obstet Gynaecol 123(2):175–178. doi:10.1111/1471-0528.13731
Stevens VL, Jacobs EJ, Patel AV, Sun J, Gapstur SM, McCullough ML (2014) Body weight in early adulthood, adult weight gain, and risk of endometrial cancer in women not using postmenopausal hormones. Cancer Causes Control 25(3):321–328. doi:10.1007/s10552-013-0333-7
Canchola AJ, Anton-Culver H, Bernstein L, Clarke CA, Henderson K, Ma H, Ursin G, Horn-Ross PL (2012) Body size and the risk of postmenopausal breast cancer subtypes in the California Teachers Study cohort. Cancer Causes Control 23:473–485. doi:10.1007/s10552-012-9897-x
Chang SC, Lacey JV Jr, Brinton LA, Hartge P, Adams K, Mouw T, Carroll L, Hollenbeck A, Schatzkin A, Leitzmann MF (2007) Lifetime weight history and endometrial cancer risk by type of menopausal hormone use in the NIH-AARP diet and health study. Cancer Epidemiol Biomark Prev 16(4):723–730. doi:10.1158/1055-9965.epi-06-0675
Crosbie EJ, Zwahlen M, Kitchener HC, Egger M, Renehan AG (2010) Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 19(12):3119–3130. doi:10.1158/1055-9965.epi-10-0832
Friedenreich C, Cust A, Lahmann PH, Steindorf K, Boutron-Ruault MC, Clavel-Chapelon F, Mesrine S, Linseisen J, Rohrmann S, Boeing H, Pischon T, Tjonneland A, Halkjaer J, Overvad K, Mendez M, Redondo ML, Garcia CM, Larranaga N, Tormo MJ, Gurrea AB, Bingham S, Khaw KT, Allen N, Key T, Trichopoulou A, Vasilopoulou E, Trichopoulos D, Pala V, Palli D, Tumino R, Mattiello A, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Berglund G, Manjer J, Lundin E, Lukanova A, Slimani N, Jenab M, Kaaks R, Riboli E (2007) Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition. Cancer Causes Control 18(4):399–413. doi:10.1007/s10552-006-0113-8
McCullough ML, Patel AV, Patel R, Rodriguez C, Feigelson HS, Bandera EV, Gansler T, Thun MJ, Calle EE (2008) Body mass and endometrial cancer risk by hormone replacement therapy and cancer subtype. Cancer Epidemiol Biomark Prev 17(1):73–79. doi:10.1158/1055-9965.epi-07-2567
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. J Am Med Assoc 288(3):321–333. doi:10.1001/jama.288.3.321
SEER Cancer Statistics Review, 1975–2012. (2015). http://seer.cancer.gov/csr/1975_2012/. Accessed April 2015
Bernstein L, Allen M, Anton-Culver H, Deapen D, Horn-Ross PL, Peel D, Pinder R, Reynolds P, Sullivan-Halley J, West D, Wright W, Ziogas A, Ross RK (2002) High breast cancer incidence rates among California teachers: results from the California Teachers Study (United States). Cancer Causes Control 13(7):625–635
Molarius A, Seidell JC (1998) Selection of anthropometric indicators for classification of abdominal fatness—a critical review. Int J Obes Relat Metab Disord 22(8):719–727
Robinson WR, Tse CK, Olshan AF, Troester MA (2014) Body size across the life course and risk of premenopausal and postmenopausal breast cancer in Black women, the Carolina Breast Cancer Study, 1993–2001. Cancer Causes Control 25(9):1101–1117. doi:10.1007/s10552-014-0411-5
Kwong SLPC, Morris CR et al (2001) Cancer in California: 1988–1999. Cancer Surveillance Section, California Department of Health Services, Sacramento
Dougan MM, Hankinson SE, Vivo ID, Tworoger SS, Glynn RJ, Michels KB (2015) Prospective study of body size throughout the life-course and the incidence of endometrial cancer among premenopausal and postmenopausal women. Int J Cancer 137(3):625–637. doi:10.1002/ijc.29427
Yang TY, Cairns BJ, Allen N, Sweetland S, Reeves GK, Beral V (2012) Postmenopausal endometrial cancer risk and body size in early life and middle age: prospective cohort study. Br J Cancer 107(1):169–175. doi:10.1038/bjc.2012.229
Brinton LA, Felix AS (2014) Menopausal hormone therapy and risk of endometrial cancer. J Steroid Biochem Mol Biol 142:83–89. doi:10.1016/j.jsbmb.2013.05.001
Razavi P, Pike MC, Horn-Ross PL, Templeman C, Bernstein L, Ursin G (2010) Long-term postmenopausal hormone therapy and endometrial cancer. Cancer Epidemiol Biomark Prev 19(2):475–483. doi:10.1158/1055-9965.epi-09-0712
Edlefsen KL, Jackson RD, Prentice RL, Janssen I, Rajkovic A, O’Sullivan MJ, Anderson G (2010) The effects of postmenopausal hormone therapy on serum estrogen, progesterone, and sex hormone-binding globulin levels in healthy postmenopausal women. Menopause 17(3):622–629. doi:10.1097/gme.0b013e3181cb49e9
Key TJ, Appleby PN, Reeves GK, Roddam AW, Helzlsouer KJ, Alberg AJ, Rollison DE, Dorgan JF, Brinton LA, Overvad K, Kaaks R, Trichopoulou A, Clavel-Chapelon F, Panico S, Duell EJ, Peeters PH, Rinaldi S, Fentiman IS, Dowsett M, Manjer J, Lenner P, Hallmans G, Baglietto L, English DR, Giles GG, Hopper JL, Severi G, Morris HA, Hankinson SE, Tworoger SS, Koenig K, Zeleniuch-Jacquotte A, Arslan AA, Toniolo P, Shore RE, Krogh V, Micheli A, Berrino F, Barrett-Connor E, Laughlin GA, Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE, Cauley JA, Lui LY, Cummings SR, Gunter MJ, Rohan TE, Strickler HD (2011) Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer 105(5):709–722. doi:10.1038/bjc.2011.254
Lu L, Risch H, Irwin ML, Mayne ST, Cartmel B, Schwartz P, Rutherford T, Yu H (2011) Long-term overweight and weight gain in early adulthood in association with risk of endometrial cancer. Int J Cancer 129(5):1237–1243. doi:10.1002/ijc.26046
Song M, Willett WC, Hu FB, Spiegelman D, Must A, Wu K, Chan AT, Giovannucci EL (2016) Trajectory of body shape across the lifespan and cancer risk. Int J Cancer 138(10):2383–2395. doi:10.1002/ijc.29981
Kaaks R, Lukanova A, Kurzer MS (2002) Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomark Prev 11(12):1531–1543
Luhn P, Dallal CM, Weiss JM, Black A, Huang WY, Lacey JV Jr, Hayes RB, Stanczyk FZ, Wentzensen N, Brinton LA (2013) Circulating adipokine levels and endometrial cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomark Prev 22(7):1304–1312. doi:10.1158/1055-9965.epi-13-0258
Pischon T, Nothlings U, Boeing H (2008) Obesity and cancer. Proc Nutr Soc 67(2):128–145. doi:10.1017/S0029665108006976
Dossus L, Lukanova A, Rinaldi S, Allen N, Cust AE, Becker S, Tjonneland A, Hansen L, Overvad K, Chabbert-Buffet N, Mesrine S, Clavel-Chapelon F, Teucher B, Chang-Claude J, Boeing H, Drogan D, Trichopoulou A, Benetou V, Bamia C, Palli D, Agnoli C, Galasso R, Tumino R, Sacerdote C, Bueno-de-Mesquita HB, van Duijnhoven FJ, Peeters PH, Onland-Moret NC, Redondo ML, Travier N, Sanchez MJ, Altzibar JM, Chirlaque MD, Barricarte A, Lundin E, Khaw KT, Wareham N, Fedirko V, Romieu I, Romaguera D, Norat T, Riboli E, Kaaks R (2013) Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort—a factor analysis. Am J Epidemiol 177(8):787–799. doi:10.1093/aje/kws309
Key TJ, Pike MC (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(2):205–212
Green J, Cairns BJ, Casabonne D, Wright FL, Reeves G, Beral V (2011) Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol 12(8):785–794. doi:10.1016/S1470-2045(11)70154-1
Rota M, Rumi F, Bagnardi V, Dal Maso L, Zucchetto A, Levi F, La Vecchia C, Tavani A (2016) Modelling body mass index and endometrial cancer risk in a pooled-analysis of three case–control studies. Br J Obstet Gynaecol 123(2):285–292. doi:10.1111/1471-0528.13717
Ju W, Kim HJ, Hankinson SE, De Vivo I, Cho E (2015) Prospective study of body fat distribution and the risk of endometrial cancer. Cancer Epidemiol 39(4):567–570. doi:10.1016/j.canep.2015.05.003
Lahmann PH, Schulz M, Hoffmann K, Boeing H, Tjonneland A, Olsen A, Overvad K, Key TJ, Allen NE, Khaw KT, Bingham S, Berglund G, Wirfalt E, Berrino F, Krogh V, Trichopoulou A, Lagiou P, Trichopoulos D, Kaaks R, Riboli E (2005) Long-term weight change and breast cancer risk: the European prospective investigation into cancer and nutrition (EPIC). Br J Cancer 93(5):582–589. doi:10.1038/sj.bjc.6602763
Acknowledgments
This work was supported by the National Cancer Institute at the National Institutes of Health (Grant R01 CA77398). The collection of cancer incidence data used in this study was supported by the California Department of Public Health (CDPH) as a part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103,885; by the National Cancer Institute’s (NCI) Surveillance, Epidemiology and End Results Program under contracts N01-PC-35136 and HHSN261201000140C awarded to the Cancer Prevention Institute of California, N02-PC-15105 and HHSN261201000034C awarded to the Public Health Institute (PHI), HHSN261201000035C University of Southern California; and the Centers for Disease Control and Prevention’s (CDCP) National Program of Cancer Registries, under agreements U55/CCR921930-02 awarded to PHI and U58DP003862-01 awarded to the CDPH. The ideas and opinions expressed herein are those of the author(s) and endorsement by the CDPH, NCI, and CDCP or their contractors and subcontractors are not intended nor should be inferred. The authors would like to thank the Steering Committee who are responsible for the formation and maintenance of the cohort within which this study was conducted.
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All procedures performed in the California Teachers Study involving human participants were in accordance with the ethnical standards of the Institutional Review Boards of the Cancer Prevention Institute of California, City of Hope National Medical Center, the University of Southern California, the University of California at Irvine, and the California Health and Human Services Agency and were in compliance with the 1964 Helsinki Declaration and its later amendments or comparable ethnical standards.
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Informed consent was obtained from all individual participants included in the study.
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Horn-Ross, P.L., Canchola, A.J., Bernstein, L. et al. Body size over the life-course and the risk of endometrial cancer: the California Teachers Study. Cancer Causes Control 27, 1419–1428 (2016). https://doi.org/10.1007/s10552-016-0820-8
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DOI: https://doi.org/10.1007/s10552-016-0820-8