Proteomic Mediators of the Obesity and Colorectal Cancer Relationship; the role of inflammation and immune response
Måns Stenlund¹ , Matthew A Lee² , Linda Vidman¹ , Björn Gylling³ , Richard Palmqvist³ , Vivian Viallon² ,
Marc J Gunter⁴ , Bethany Van Guelpen^1,5
1 Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden
2 International Agency for Research on Cancer, World Health Organisation, Lyon, France
3 Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
4 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
5 Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.

Background: High body fatness is an established risk factor for colorectal cancer (CRC), but the biology is incompletely understood. Several mechanisms are believed to be involved, one of which is inflammation. Objectives: The aim of this study is to investigate circulating proteins involved in inflammation and immune response as potential mediators of the link between high body fatness and CRC risk.

Methods: This is a nested case-control study of two cohorts, the Northern Sweden Health and Disease Study (NSHDS) and the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma samples from 606 case-control pairs in NSHDS and 710 in EPIC were analysed using the Olink ® 92-protein Immuno-Oncology panel. In another 195 sample pairs from NSHDS and a subset of 220 EPIC pairs, we also ran the 1536-protein Olink ® Explore panel. Preliminary statistical analyses have been conducted using the NSHDS Immuno-Oncology data. We estimated the association between BMI, circulating proteins and subsequent CRC risk using multivariable linear and conditional logistic regression, followed by formal mediation analyses.

Preliminary results: In the NSHDS dataset, BMI was associated with 33 proteins in the ImmunoOncology panel. Of these, six were associated with subsequent CRC risk. However, in formal mediation analyses, none showed mediating effects in the relationship between BMI and CRC risk.

Conclusion: Preliminary results in the NSHDS do not support a role of circulating proteins involved in inflammation and immune-response as mediators of the link between high body fatness and CRC. Next steps are to run the statistical analyses on the Olink ® Explore panel in NSHDS and to replicate all analyses in EPIC. Exploratory subtype analyses on tumor-related factors, including anatomical location and molecular tumor subtypes, are also planned