| Title: | Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization |
| Journal: | Communications Biology |
| Published: | 8 Apr 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35396499/ |
| DOI: | https://doi.org/10.1038/s42003-022-03272-5 |
| URL: | https://www.nature.com/articles/s42003-022-03272-5.pdf |
| Citations: | 18 (14 in last 2 years) as of 8 Aug 2024 |
Publication 12422
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Abstract
Studies suggest that adiposity in childhood may reduce the risk of breast cancer in later life. The biological mechanism underlying this effect is unclear but is likely to be independent of body size in adulthood. Using a Mendelian randomization framework, we investigate 18 hypothesised mediators of the protective effect of childhood adiposity on later-life breast cancer, including hormonal, reproductive, physical, and glycaemic traits. Our results indicate that, while most of the hypothesised mediators are affected by childhood adiposity, only IGF-1 (OR: 1.08 [1.03: 1.15]), testosterone (total/free/bioavailable ~ OR: 1.12 [1.05: 1.20]), age at menopause (OR: 1.05 [1.03: 1.07]), and age at menarche (OR: 0.92 [0.86: 0.99], direct effect) influence breast cancer risk. However, multivariable Mendelian randomization analysis shows that the protective effect of childhood body size remains unaffected when accounting for these traits (ORs: 0.59-0.67). This suggests that none of the investigated potential mediators strongly contribute to the protective effect of childhood adiposity on breast cancer risk individually. It is plausible, however, that several related traits could collectively mediate the effect when analysed together, and this work provides a compelling foundation for investigating other mediating pathways in future studies.</p>
10 Keywords
- Adiposity
- Adult
- Body Mass Index
- Breast Neoplasms
- Female
- Humans
- Mendelian Randomization Analysis
- Pediatric Obesity
- Polymorphism, Single Nucleotide
- Risk Factors
6 Authors
- Marina Vabistsevits
- George Davey Smith
- Eleanor Sanderson
- Tom G. Richardson
- Bethan Lloyd-Lewis
- Rebecca C. Richmond
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