Understanding risk factors for endometrial cancer in young women

Noah Charles Peeri; Kimberly A. Bertrand; Renhua Na; Immaculata De Vivo; Veronica Wendy Setiawan; Venkatraman E. Seshan; Laia Alemany; Yu Chen; Megan A. Clarke; Tess Clendenen; Linda S. Cook; Laura Costas; Luigino Dal Maso; Jo L. Freudenheim; Christine M. Friedenreich; Gretchen L. Gierach; Marc T. Goodman; Carlo La Vecchia; Fabio Levi; Marta Lopez-Querol; Lingeng Lu; Kirsten B. Moysich; George Mutter; Jeffin Naduparambil; Eva Negri; Kelli O’Connell; Tracy O’Mara; Julie R. Palmer; Fabio Parazzini; Kathryn Lee Penney; Stacey Petruzella; Peggy Reynolds; Fulvio Ricceri; Harvey Risch; Thomas E. Rohan; Carlotta Sacerdote; Sven Sandin; Xiao Ou Shu; Rachael Z. Stolzenberg-Solomon; Penelope M. Webb; Nicolas Wentzensen; Lynne R. Wilkens; Wanghong Xu; Herbert Yu; Anne Zeleniuch-Jacquotte; Wei Zheng; Xingyi Guo; Loren Lipworth; Mengmeng Du

doi:10.1093/jnci/djae210

Understanding risk factors for endometrial cancer in young women

Noah Charles Peeri, Kimberly A. Bertrand, Renhua Na, Immaculata De Vivo, Veronica Wendy Setiawan, Venkatraman E. Seshan, Laia Alemany, Yu Chen, Megan A. Clarke, Tess Clendenen, Linda S. Cook, Laura Costas, Luigino Dal Maso, Jo L. Freudenheim, Christine M. Friedenreich, Gretchen L. Gierach, Marc T. Goodman, Carlo La Vecchia, Fabio Levi, Marta Lopez-QuerolLingeng Lu, Kirsten B. Moysich, George Mutter, Jeffin Naduparambil, Eva Negri, Kelli O’Connell, Tracy O’Mara, Julie R. Palmer, Fabio Parazzini, Kathryn Lee Penney, Stacey Petruzella, Peggy Reynolds, Fulvio Ricceri, Harvey Risch, Thomas E. Rohan, Carlotta Sacerdote, Sven Sandin, Xiao Ou Shu, Rachael Z. Stolzenberg-Solomon, Penelope M. Webb, Nicolas Wentzensen, Lynne R. Wilkens, Wanghong Xu, Herbert Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Xingyi Guo, Loren Lipworth, Mengmeng Du

Urban Initiative

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. Methods: We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. Results: In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (P_het < .01). Body mass index was the strongest risk factor (OR_≥ 35 vs <25 kg=_m2 ¼ 5.57, 95% CI ¼ 4.33 to 7.16, for ages younger than 50 years; OR_≥ 35 vs <25 kg=_m2 ¼ 4.68, 95% CI ¼ 4.30 to 5.09, for ages 50 years and older; P_het ¼ .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (P_het < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. Conclusions: Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.

Original language	English (US)
Pages (from-to)	76-88
Number of pages	13
Journal	Journal of the National Cancer Institute
Volume	117
Issue number	1
DOIs	https://doi.org/10.1093/jnci/djae210
State	Published - Jan 1 2025

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1093/jnci/djae210

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Peeri, N. C., Bertrand, K. A., Na, R., Vivo, I. D., Setiawan, V. W., Seshan, V. E., Alemany, L., Chen, Y., Clarke, M. A., Clendenen, T., Cook, L. S., Costas, L., Maso, L. D., Freudenheim, J. L., Friedenreich, C. M., Gierach, G. L., Goodman, M. T., Vecchia, C. L., Levi, F., ... Du, M. (2025). Understanding risk factors for endometrial cancer in young women. Journal of the National Cancer Institute, 117(1), 76-88. https://doi.org/10.1093/jnci/djae210

Peeri, NC, Bertrand, KA, Na, R, Vivo, ID, Setiawan, VW, Seshan, VE, Alemany, L, Chen, Y, Clarke, MA, Clendenen, T, Cook, LS, Costas, L, Maso, LD, Freudenheim, JL, Friedenreich, CM, Gierach, GL, Goodman, MT, Vecchia, CL, Levi, F, Lopez-Querol, M, Lu, L, Moysich, KB, Mutter, G, Naduparambil, J, Negri, E, O’Connell, K, O’Mara, T, Palmer, JR, Parazzini, F, Penney, KL, Petruzella, S, Reynolds, P, Ricceri, F, Risch, H, Rohan, TE, Sacerdote, C, Sandin, S, Shu, XO, Stolzenberg-Solomon, RZ, Webb, PM, Wentzensen, N, Wilkens, LR, Xu, W, Yu, H, Zeleniuch-Jacquotte, A, Zheng, W, Guo, X, Lipworth, L & Du, M 2025, 'Understanding risk factors for endometrial cancer in young women', Journal of the National Cancer Institute, vol. 117, no. 1, pp. 76-88. https://doi.org/10.1093/jnci/djae210

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title = "Understanding risk factors for endometrial cancer in young women",

abstract = "Background: The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. Methods: We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. Results: In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet < .01). Body mass index was the strongest risk factor (OR≥ 35 vs <25 kg=m2 ¼ 5.57, 95% CI ¼ 4.33 to 7.16, for ages younger than 50 years; OR≥ 35 vs <25 kg=m2 ¼ 4.68, 95% CI ¼ 4.30 to 5.09, for ages 50 years and older; Phet ¼ .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. Conclusions: Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.",

author = "Peeri, {Noah Charles} and Bertrand, {Kimberly A.} and Renhua Na and Vivo, {Immaculata De} and Setiawan, {Veronica Wendy} and Seshan, {Venkatraman E.} and Laia Alemany and Yu Chen and Clarke, {Megan A.} and Tess Clendenen and Cook, {Linda S.} and Laura Costas and Maso, {Luigino Dal} and Freudenheim, {Jo L.} and Friedenreich, {Christine M.} and Gierach, {Gretchen L.} and Goodman, {Marc T.} and Vecchia, {Carlo La} and Fabio Levi and Marta Lopez-Querol and Lingeng Lu and Moysich, {Kirsten B.} and George Mutter and Jeffin Naduparambil and Eva Negri and Kelli O{\textquoteright}Connell and Tracy O{\textquoteright}Mara and Palmer, {Julie R.} and Fabio Parazzini and Penney, {Kathryn Lee} and Stacey Petruzella and Peggy Reynolds and Fulvio Ricceri and Harvey Risch and Rohan, {Thomas E.} and Carlotta Sacerdote and Sven Sandin and Shu, {Xiao Ou} and Stolzenberg-Solomon, {Rachael Z.} and Webb, {Penelope M.} and Nicolas Wentzensen and Wilkens, {Lynne R.} and Wanghong Xu and Herbert Yu and Anne Zeleniuch-Jacquotte and Wei Zheng and Xingyi Guo and Loren Lipworth and Mengmeng Du",

year = "2025",

month = jan,

day = "1",

doi = "10.1093/jnci/djae210",

language = "English (US)",

volume = "117",

pages = "76--88",

journal = "Journal of the National Cancer Institute",

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TY - JOUR

T1 - Understanding risk factors for endometrial cancer in young women

AU - Peeri, Noah Charles

AU - Bertrand, Kimberly A.

AU - Na, Renhua

AU - Vivo, Immaculata De

AU - Setiawan, Veronica Wendy

AU - Seshan, Venkatraman E.

AU - Alemany, Laia

AU - Chen, Yu

AU - Clarke, Megan A.

AU - Clendenen, Tess

AU - Cook, Linda S.

AU - Costas, Laura

AU - Maso, Luigino Dal

AU - Freudenheim, Jo L.

AU - Friedenreich, Christine M.

AU - Gierach, Gretchen L.

AU - Goodman, Marc T.

AU - Vecchia, Carlo La

AU - Levi, Fabio

AU - Lopez-Querol, Marta

AU - Lu, Lingeng

AU - Moysich, Kirsten B.

AU - Mutter, George

AU - Naduparambil, Jeffin

AU - Negri, Eva

AU - O’Connell, Kelli

AU - O’Mara, Tracy

AU - Palmer, Julie R.

AU - Parazzini, Fabio

AU - Penney, Kathryn Lee

AU - Petruzella, Stacey

AU - Reynolds, Peggy

AU - Ricceri, Fulvio

AU - Risch, Harvey

AU - Rohan, Thomas E.

AU - Sacerdote, Carlotta

AU - Sandin, Sven

AU - Shu, Xiao Ou

AU - Stolzenberg-Solomon, Rachael Z.

AU - Webb, Penelope M.

AU - Wentzensen, Nicolas

AU - Wilkens, Lynne R.

AU - Xu, Wanghong

AU - Yu, Herbert

AU - Zeleniuch-Jacquotte, Anne

AU - Zheng, Wei

AU - Guo, Xingyi

AU - Lipworth, Loren

AU - Du, Mengmeng

PY - 2025/1/1

Y1 - 2025/1/1

N2 - Background: The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. Methods: We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. Results: In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet < .01). Body mass index was the strongest risk factor (OR≥ 35 vs <25 kg=m2 ¼ 5.57, 95% CI ¼ 4.33 to 7.16, for ages younger than 50 years; OR≥ 35 vs <25 kg=m2 ¼ 4.68, 95% CI ¼ 4.30 to 5.09, for ages 50 years and older; Phet ¼ .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. Conclusions: Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.

AB - Background: The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. Methods: We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. Results: In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet < .01). Body mass index was the strongest risk factor (OR≥ 35 vs <25 kg=m2 ¼ 5.57, 95% CI ¼ 4.33 to 7.16, for ages younger than 50 years; OR≥ 35 vs <25 kg=m2 ¼ 4.68, 95% CI ¼ 4.30 to 5.09, for ages 50 years and older; Phet ¼ .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. Conclusions: Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.

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DO - 10.1093/jnci/djae210

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SP - 76

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JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

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ER -

Understanding risk factors for endometrial cancer in young women

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