Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium

Abstract

Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (P(trend) < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years.

Figure 1.

The risk of endometrial cancer associated with a 5-year increase in age at last birth by study. The numbers of cases and controls shown in each study were after all exclusions had been applied. Odds ratios were stratified by age and race/ethnicity and, when possible, were adjusted for parity, age at menarche, body mass index, oral contraceptive use, menopausal hormone use, smoking, and diabetes. The combined odds ratio per 5-year increase of 0.88 (95% confidence interval: 0.85, 0.91) was calculated using a random-effects model with a P for heterogeneity of 0.12. ANECS, Australian National Endometrial Cancer Study; BAWHS, Bay Area Women's Health Study; BCDDP, Breast Cancer Detection Demonstration Project; CECS, Connecticut Endometrial Cancer Study; CI, confidence interval; CTS, California Teachers Study; EDGE, Estrogen, Diet, Genetics, and Endometrial Cancer Study; FHCRC, Fred Hutchinson Cancer Research Center Study; HAW, Hawaii Endometrial Cancer Study; IWHS, Iowa Women's Health Study; NHS, Nurses' Health Study; PECS, Polish Endometrial Cancer Study; PEDS, Patient Epidemiologic Data System Study; SECS, Shanghai Endometrial Cancer Study; US, US Endometrial Cancer Study; USC, case-control study conducted by USC; WISE, Women's Insight and Shared Experience Study; and WNYDS, Western New York Diet Study.