Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium

Susan J Jordan; Renhua Na; Elisabete Weiderpass; Hans-Olov Adami; Kristin E Anderson; Piet A van den Brandt; Louise A Brinton; Chu Chen; Linda S Cook; Jennifer A Doherty; Mengmeng Du; Christine M Friedenreich; Gretchen L Gierach; Marc T Goodman; Vittorio Krogh; Fabio Levi; Lingeng Lu; Anthony B Miller; Susan E McCann; Kirsten B Moysich; Eva Negri; Sara H Olson; Stacey Petruzella; Julie R Palmer; Fabio Parazzini; Malcolm C Pike; Anna E Prizment; Timothy R Rebbeck; Peggy Reynolds; Fulvio Ricceri; Harvey A Risch; Thomas E Rohan; Carlotta Sacerdote; Leo J Schouten; Diego Serraino; Veronica W Setiawan; Xiao-Ou Shu; Todd R Sponholtz; Amanda B Spurdle; Rachael Z Stolzenberg-Solomon; Britton Trabert; Nicolas Wentzensen; Lynne R Wilkens; Lauren A Wise; Herbert Yu; Carlo La Vecchia; Immaculata De Vivo; Wanghong Xu; Anne Zeleniuch-Jacquotte; Penelope M Webb

doi:10.1002/ijc.33360

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium

Jordan SJ, Na R, Weiderpass E, Adami HO, Anderson KE, van den Brandt PA, Brinton LA, Chen C, Cook LS, Doherty JA, Du M, Friedenreich CM, Gierach GL, Goodman MT, Krogh V, Levi F, Lu L, Miller AB, McCann SE, Moysich KB, Negri E, Olson SH, Petruzella S, Palmer JR, Parazzini F, Pike MC, Prizment AE, Rebbeck TR, Reynolds P, Ricceri F, Risch HA, Rohan TE, Sacerdote C, Schouten LJ, Serraino D, Setiawan VW, Shu XO, Sponholtz TR, Spurdle AB, Stolzenberg-Solomon RZ, Trabert B, Wentzensen N, Wilkens LR, Wise LA, Yu H, La Vecchia C, De Vivo I, Xu W, Zeleniuch-Jacquotte A, Webb PM

Published May 2021 International journal of cancer, 148(9), 2068-2078

DOI 10.1002/ijc.33360 PMID 33105052 PMC PMC7969437

RRM Academy Synopsis

Endometrial cancer risk was lower with each additional pregnancy

A pooled analysis of 30 observational studies of women found that endometrial cancer risk was lower with each full-term pregnancy, about 15% per birth. The data included 16,986 women diagnosed with endometrial cancer and 39,538 control women. Incomplete pregnancies were also linked to lower risk, by a smaller amount.

Key Findings

The reduction in risk appeared largest after a woman's first full-term birth (OR=0.78, 95%CI 0.72–0.84).
Later births were each linked to about 15% lower risk on average (OR=0.85, 95%CI 0.84–0.87). The estimate at eight births was OR=0.20, 95%CI 0.14–0.28.
Lower risk held in every group of women, whatever their age at the last full-term pregnancy.
Each incomplete pregnancy was linked to 9% lower risk, at OR=0.91 with 95%CI 0.88–0.95. Any spontaneous abortion gave OR=0.83, 95%CI 0.76–0.90, and any induced abortion gave OR=0.89, 95%CI 0.79–1.01.
In this analysis, women with twin or multiple births showed the same association as women with only singleton births.

Interpretation

The work combines participant-level records from 30 studies: 11 cohorts and 19 case-control designs. Women reported their own pregnancy histories. The association appeared stronger in younger women, in white women than in black women, and for type 1 than type 2 cancers. The authors state that women recall incomplete pregnancies less reliably than births. They discuss hormonal and endometrial-shedding explanations, and the mechanism stays unclear.

RRM Context

Restorative reproductive medicine works with hormonal function. The paper links pregnancy history to endometrial cancer risk, and its authors point to progesterone, lower estradiol and shedding of the uterine lining as possible reasons. Risk was also lower after a lost pregnancy, so the authors see little cause to fear that a loss harms the uterine lining where cancer is concerned.

Our editorial summary of this paper, not the article's abstract.

Abstract

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Topics

General Gynecology

Gynecologic Oncology Endometrial Cancer

General Gynecology › Gynecologic Oncology › Endometrial Cancer

Susan J Jordan, Renhua Na, Elisabete Weiderpass, Hans-Olov Adami, Kristin E Anderson, Piet A van den Brandt, Louise A Brinton, Chu Chen, Linda S Cook, Jennifer A Doherty, Mengmeng Du, Christine M Friedenreich, Gretchen L Gierach, Marc T Goodman, Vittorio Krogh, Fabio Levi, Lingeng Lu, Anthony B Miller, Susan E McCann, Kirsten B Moysich, Eva Negri, Sara H Olson, Stacey Petruzella, Julie R Palmer, Fabio Parazzini, Malcolm C Pike, Anna E Prizment, Timothy R Rebbeck, Peggy Reynolds, Fulvio Ricceri, Harvey A Risch, Thomas E Rohan, Carlotta Sacerdote, Leo J Schouten, Diego Serraino, Veronica W Setiawan, Xiao-Ou Shu, Todd R Sponholtz, Amanda B Spurdle, Rachael Z Stolzenberg-Solomon, Britton Trabert, Nicolas Wentzensen, Lynne R Wilkens, Lauren A Wise, Herbert Yu, Carlo La Vecchia, Immaculata De Vivo, Wanghong Xu, Anne Zeleniuch-Jacquotte, Penelope M Webb

Sue Jordan, S Jordan, R Na, E Weiderpass, H Adami, K Anderson, P Brandt, L Brinton, C Chen, L Cook, Jen Doherty, Jenny Doherty, J Doherty, M Du, Chris Friedenreich, C Friedenreich, G Gierach, M Goodman, V Krogh, F Levi, L Lu, Tony Miller, A Miller, Sue McCann, S McCann, K Moysich, E Negri, S Olson, S Petruzella, J Palmer, F Parazzini, M Pike, A Prizment, Tim Rebbeck, T Rebbeck, Margaret Reynolds, P Reynolds, F Ricceri, H Risch, Tom Rohan, T Rohan, C Sacerdote, L Schouten, D Serraino, V Setiawan, X Shu, T Sponholtz, A Spurdle, R Stolzenberg-Solomon, B Trabert, N Wentzensen, L Wilkens, L Wise, H Yu, C Vecchia, I Vivo, W Xu, A Zeleniuch-Jacquotte, P Webb

PMID 33105052 33105052 DOI 10.1002/ijc.33360 10.1002/ijc.33360 Jordan et al. 2021, Jordan 2021

Keywords

endometrial cancer, induced abortion, miscarriage, parity, sex of offspring

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium

Endometrial cancer risk was lower with each additional pregnancy

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Related research

Keywords