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Mammographic density mediates the protective effect of early-life body size on breast cancer risk

  • 0University of Bristol, MRC Integrative Epidemiology Unit, Bristol, UK. marina.vabistsevits@bristol.ac.uk.
Nature Communications +

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May 13, 2024

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May 13, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Childhood adiposity lowers mammographic dense area, reducing breast cancer risk. This protective effect is significantly mediated by changes in dense area, highlighting a key mechanism for breast cancer prevention.

Area Of Science

  • Reproductive epidemiology
  • Genetics
  • Cancer research

Background

  • Childhood adiposity is linked to reduced breast cancer risk, but the underlying mechanisms are unclear.
  • Mammographic density (MD) is a strong breast cancer risk factor, and its relationship with adiposity and puberty is complex.

Purpose Of The Study

  • To investigate the complex interplay between childhood and adulthood adiposity, puberty onset, mammographic density phenotypes, and breast cancer risk.
  • To elucidate the mediating role of mammographic density in the protective effect of childhood adiposity on breast cancer.

Main Methods

  • Utilized Mendelian randomization (MR) and multivariable MR to assess causal effects.
  • Analyzed relationships between adiposity, age at menarche, and mammographic density phenotypes (dense area, non-dense area, percent density).
  • Employed mediation MR analysis to quantify the role of mammographic density in the adiposity-breast cancer link.

Main Results

  • Childhood adiposity decreased dense area, while adulthood adiposity increased non-dense area.
  • Later menarche was associated with increased dense area/percent density, but this effect was attenuated by childhood adiposity.
  • Dense area and percent density were associated with increased breast cancer risk across all subtypes.
  • Mediation analysis revealed that 56% of the protective effect of childhood adiposity on breast cancer risk was mediated via dense area.

Conclusions

  • Higher childhood adiposity reduces mammographic dense area, which in turn lowers breast cancer risk.
  • Mammographic density, particularly dense area, plays a significant mediating role in the protective effect of early-life adiposity.
  • Understanding this pathway offers potential targets for breast cancer intervention strategies.