Genetic variants enriched in the brain and adipose tissue may link adiposity subtypes to colorectal cancer

A new study published in Science Advances has found that having an overall obese body shape or a tall, centrally obese body shape increases the risk of colorectal cancer by more than 10%. This study’s genetic analysis discovered that these two distinct adiposity subtypes differ in their tissue-specific gene expression. Genes that are overexpressed in certain brain regions and genes that are overexpressed mainly in adipose tissue could link these two adiposity subtypes to the development of colorectal cancer.

This is the largest study of its kind and was led by Dr Heinz Freisling, a cancer epidemiologist at the International Agency for Research on Cancer (IARC), in collaboration with researchers from the University of Regensburg (Germany), the Institut d’Investigació Biomèdica de Girona (IDIBGI) (Spain), Imperial College London (United Kingdom), and other partner institutions. The researchers investigated the association between four distinct body shapes and the risk of colorectal cancer and unravelled potential mechanisms in the development of colorectal cancer by examining the role of tissue-specific gene expression of the body shapes.

The researchers gathered data from more than 550 000 adults, who participated in the UK Biobank and in a large consortium that collected genetic information from adults with and without colorectal cancer. In addition, gene expression data at the human tissue level from more than 800 donors were integrated to identify genetic associations with body shapes. Previous research had not combined data from observational and genetic studies in this way to answer the question of how adiposity subtypes are linked to colorectal cancer.

Peruchet-Noray L, Sedlmeier AM, Dimou N, Baurecht H, Fervers B, Fontvieille E, et al.
Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer
Sci Adv, Published online 19 April 2024;
https://doi.org/10.1126/sciadv.adj1987

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