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 = 5.57, 95% CI = 4.33 to 7.16, for ages younger than 50 years; OR≥35 vs<25 kg/m2 = 4.68, 95% CI = 4.30 to 5.09, for ages 50 years and older; Phet = .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.

Figure 1.

Fully adjusted multivariable association between risk factors and early onset endometrial cancer and late-onset endometrial cancer risk. Multivariable models included age, race, study site, body mass index, age at menarche, parity, oral contraceptive use, smoking status, postmenopausal hormone use, and diabetes status. LL = lower limit; OR = odds ratio; UL = upper limit.

Figure 2.

The association between the combined risk factor score and endometrial cancer risk stratified by age. The model was adjusted for age, race, study site, and postmenopausal hormone use. EC = endometrial cancer; het = heterogeneity.

Figure 3.

Age-specific proportion of endometrial cancers attributable to key risk factors in the Epidemiology of Endometrial Cancer Consortium. The population attributable fraction is an estimate of the proportion of endometrial cancers that would not occur if the risk factor was absent, adjusting for other covariates (age, race, study site, body mass index, age at menarche, parity, oral contraceptive use, smoking status, postmenopausal hormone use, and diabetes status). BMI = body mass index; OC = oral contraceptive.