Amadou, Amina and Freisling, Heinz and Sedlmeier, Anja M. and Bohmann, Patricia and Fontvieille, Emma and Weber, Andrea and Konzok, Julian and Stein, Michael J. and Peruchet-Noray, Laia and Jansana, Anna and Noh, Hwayoung and His, Mathilde and Gan, Quan and Baurecht, Hansjoerg and Fervers, Beatrice (2024) Multi-Trait Body Shape Phenotypes and Breast Cancer Risk in Postmenopausal Women: A Causal Mediation Analysis in the UK Biobank Cohort. JOURNAL OF EPIDEMIOLOGY AND GLOBAL HEALTH, 14 (2). pp. 420-432. ISSN 2210-6006, 2210-6014
Full text not available from this repository. (Request a copy)Abstract
Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OBESITY; METAANALYSIS; METABOLISM; Breast cancer; Anthropometry; Body shape; Biomarker; Mediation; Interaction |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Nov 2025 09:45 |
| Last Modified: | 05 Nov 2025 09:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64933 |
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