Childhood body mass index trajectories and subtypes of endometrial cancer: A Danish cohort study

Background Obesity in adulthood is a well-established risk factor for endometrial cancer, a heterogeneous disease comprising several histological subtypes. Although childhood body mass index (BMI) is linked to endometrial cancer, the role of childhood growth patterns in different subtypes is unclear. Therefore, we investigated the associations between childhood BMI trajectories and endometrial cancer subtypes. Methods We included 167,682 females from the Copenhagen School Health Records Register, born 1930–1996. Five BMI trajectories (‘below-average’, ‘average’, ‘above-average’, ‘overweight’, and ‘obesity’) were modelled on repeated weight and height measurements at ages 6–15 years. Outcome data were obtained from the Danish Cancer Registry (1978–2022). Associations between BMI trajectories and endometrial cancer subtypes were estimated using Cox regression models. Cumulative incidence of endometrial cancer by childhood BMI trajectory was assessed using the Aalen-Johansen estimator. Results During follow-up, 1703 females were diagnosed with endometrial cancer, of which 1420 were endometrioid and 260 non-endometrioid. All trajectories with above average BMI levels showed an increased hazard ratio of endometrioid endometrial cancer compared with the average trajectory. The hazard ratios increased with higher BMI trajectories with a hazard ratio of 3.04 (95% confidence interval: 2.29–4.02) for the obesity trajectory. A similar, but non-significant trend was observed for non-endometrioid tumors. The cumulative incidence of endometrial cancer increased with higher BMI trajectories; from 65 years and onwards, all trajectories with above average BMI levels had a significantly increased risk of endometrial cancer. Conclusion All trajectories with above average BMI levels in childhood were associated with elevated hazards of endometrioid endometrial cancer, whereas childhood obesity increased the hazard for both endometrioid and non-endometrioid endometrial cancer. These findings suggest that childhood BMI development may be an early marker of later endometrial cancer risk.