Body shape phenotypes and breast cancer risk: a Mendelian randomization analysis

In a new study, scientists from the International Agency for Research on Cancer (IARC) and partner institutions investigate the association between three distinct body shape phenotypes and breast cancer risk. The study was published in the journal Cancers.

The body shape phenotypes were derived from height, weight, body mass index, waist and hip circumference, and waist-to-hip ratio by a principal component analysis. Genetic variants robustly linked to these body shapes were extracted from a previous genome-wide association study. Summary statistics for these genetic variants were obtained from 133 384 cases and 113 789 controls of European descent in the Breast Cancer Association Consortium and combined in a two-sample Mendelian randomization analysis to investigate associations with breast cancer risk.

A body shape characterized by genetically predicted overall adiposity was inversely associated with overall breast cancer risk (odds ratio per one standard deviation, 0.89; 95% confidence interval, 0.81–0.98). This inverse association is probably because the genetic variants that predict this body shape reflect body fatness during childhood and adolescence rather than during later adulthood, when it has been shown that an adipose body shape increases the risk of breast cancer and other cancer types. A body shape characterized by tall stature with low waist-to-hip ratio was weakly positively associated with overall breast cancer risk (odds ratio, 1.05; 95% confidence interval, 0.98–1.12). A body shape characterized by tall stature with high waist-to-hip ratio was not associated with breast cancer risk.

These findings provide evidence for potential causal associations between body shape and breast cancer risk and may spur wider application in cancer research and possibly risk stratification.

Peruchet-Noray L, Dimou N, Sedlmeier AM, Fervers B, Romieu I, Viallon V, et al.
Body shape phenotypes and breast cancer risk: a Mendelian randomization analysis
Cancers, Published online 17 February 2023;
https://doi.org/10.3390/cancers15041296

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