Abstract
Increased adiposity is a known risk factor for endometrial cancer (EC). This study aimed to disentangle the separate causal roles of child and adult adiposity on EC risk in adults, including endometrioid and non-endometrioid histological subtypes using multivariable Mendelian randomisation. These analyses employed genetic associations derived from UK Biobank as proxies for child and adult body size in 12,906 cases and 108,979 controls that participated in the Endometrial Cancer Association Consortium. In multivariable analyses, adult body size increased overall EC (OR 2.30, 95% CI 1.73–3.06) and endometrioid EC risk (OR 2.28, 95% CI 1.65–3.16), while child body size had minimal effect. In contrast, child body size (OR 2.26, 95% CI 1.03–4.99) but not adult body size increased non-endometrioid EC risk. As such, child adiposity has an indirect effect on endometrioid EC risk that is mediated by adult adiposity but has a direct effect on non-endometrioid EC risk that is independent of adult adiposity. These novel findings indicate that interventions targeting adiposity during distinct periods in life have a critical role in preventing subtype-specific EC.
| Original language | English |
|---|---|
| Pages (from-to) | 87–90 |
| Number of pages | 4 |
| Journal | International Journal of Obesity |
| Volume | 47 |
| Issue number | 1 |
| Early online date | 10 Nov 2022 |
| DOIs | |
| Publication status | Published - 1 Jan 2023 |
Bibliographical note
Publisher Copyright:© 2022, The Author(s).
Access to Document
- Full-text PDF (final published version)
This is the final published version of the article (version of record). It first appeared online via Springer Nature at https://doi.org/10.1038/s41366-022-01231-y . Please refer to any applicable terms of use of the publisher.