Adiposity in Childhood May Affect the Risk of Developing Breast Cancer in Adulthood

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The study data demonstrate that higher adiposity in childhood results in less dense breast tissue forming, reducing the risk of breast cancer.

Breast cancer mammogram -- Image credit: okrasiuk | stock.adobe.com

Image credit: okrasiuk | stock.adobe.com

According to new research, higher adiposity in childhood may lead to less dense breast tissue forming, resulting in a lower risk of developing breast cancer. Rates in breast cancer, which is 1 of the most common cancers in women, continue to increase, therefore, there is a need to identify new risk factors that are modifiable.1

For this study, the authors investigated the potential role of mammographic density (MD) in the protective effect of childhood adiposity on breast cancer risk. The investigators examined the effect of body size in both childhood and adulthood on mammographic density (eg, dense area, non-dense area, percent density) using univariable Mendelian randomization and multivariable Mendelian randomization (MVMR). Additionally, the role of age at menarche in the childhood body size effect on MD phenotypes was also reviewed, as well as the effect they have on breast cancer risk.2

The investigators observed evidence that suggested that a larger body size—during both childhood and adulthood—reduces dense area (childhood: −0.63 [95% CI −0.76: −0.49]; adulthood: −0.51 [95% CI −0.63: −0.38]) and percent density (childhood: −0.88 [95% CI −1.01: −0.74]; adulthood: −0.95 [95% CI −1.06: −0.83]), but it increases non-dense area (childhood: 0.81 [95% CI 0.67: 0.96]; adulthood: 1.08 [95% CI 0.97: 1.19]).2

Additionally, the authors also observed a direct effect of body size at both ages on MD conditional on the other age, with larger childhood body size having a strong effect on decreasing dense area (−0.53 [−0.70: −0.37] vs -0.21 [−0.37: −0.05], respectively), whereas larger adult body size had a stronger influence on increasing non-dense area, or the adipose tissue area of the breast (0.28 [0.12: 0.44] vs 0.93 [0.77: 1.08]). According to the investigators, a higher body size during childhood—notably around the start of puberty—leads to less dense tissue forming in the breast, where cancer would normally develop.1,2

Further, there was a consistent trend present in the direction of effect across all breast cancer subtypes for each MD exposure trait. Dense area and percent density were shown to increase the risk, whereas non-dense area decreased the risk. Despite the consistency, the investigators noted that there was stronger evidence that suggested a positive effect of dense area on overall breast cancer (OR 1.38 [95% CI 1.002: 1.90]), and ER+ breast cancer, along with several subtypes.2

Limitations of the study include the precision of estimates and pathway analysis, small sample size, and the low number of robustly associated genetic instruments used in the analysis. The authors note that even though having a less dense area within the breast appeared to lead to a reduced risk of breast cancer during adulthood, the biological mechanism and pathway is likely more complex. Identifying smaller steps within the process using genetic data can be significant in detecting the source of this association. The authors note that, despite the findings, additional research must be conducted—particularly with a larger sample size—to further understand the mechanism of the overall protective effect of childhood adiposity to identify more targets for both intervention and prevention.1,2

“Studying the mechanism of childhood adiposity protective effect is important, as weight gain in childhood cannot be considered to be a preventative measure for breast cancer,” said corresponding author Marina Vabistsevits, University of Bristol’s MRC Integrative Epidemiology Unit and Bristol Medical School, Population Health Sciences, in a press release. "Investigating how this overall ‘protection’ works is crucial to understand the underlying mechanisms leading to and preventing cancer, as it might help identify new targets for intervention and prevention."1

References
1. University of Bristol. Adiposity in childhood affects the risk of breast cancer by changing breast tissue composition, study suggests. News release. May 14, 2024. Accessed May 15, 2024. https://www.eurekalert.org/news-releases/1044628
2. Vabistsevits, M, Davey Smith, G, Richardson, TG, et al. Mammographic density mediates the protective effect of early-life body size on breast cancer risk. Nat Commun 15, 4021 (2024) doi:10.1038/s41467-024-48105-7
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