Why does food increase or decrease the risk of colorectal cancer?

This research will aim to identify mechanistic pathways linking diet to colorectal cancer

  • Topic: Colorectal cancer
  • Institution: Imperial College London
  • Country: United Kingdom
  • Status: Ongoing
Researcher: Konstantinos Tsilidis
  • Grant awarded: November 2020

I’m delighted that my research project on identifying mechanistic pathways linking diet to colorectal cancer (CRC) was funded by WCRF. The proposed investigation will integrate dietary intake data with tumour molecular characteristics, germline genetic variation and metabolomic profiling, which will give novel insights into the role of dietary exposures in CRC development. Such insights, especially new evidence on biological mechanisms linking diet to CRC, can help optimize prevention measures, aid the establishment of future food/nutrient trials or trials on new therapeutic agents, and will inform public health messages aimed at reducing the burden of CRC.

– Konstantinos Tsilidis

Background

Studies on large populations suggest that several dietary factors are associated with a reduced or increased risk of colorectal cancer. The Third Expert Report by the World Cancer Research Fund (WCRF) identified strong evidence that eating wholegrains, dietary fibre, and dairy products reduces the risk of colorectal cancer, whereas eating red meat, processed meat, and alcohol increases the risk. However, the biological causes underlying the link between diet and colorectal cancer are poorly understood. Understanding these biological mechanisms would permit development of specific interventions for individuals at risk of developing colorectal cancer.

Aims and objectives

We aim to understand more about how diet is associated with colorectal cancer development on a molecular and cellular level. We will look at dietary factors that WCRF has identified as being strongly linked to colorectal cancer, namely: wholegrains, dietary fibre, dairy products, red and processed meat, and alcohol. We hypothesise that numerous biological causes will be found.

How it will be done

Examine the link between various food products and the risk of specific colorectal cancer subtypes in a large sample of the population. We will then explore genetic pathways that may cause this link, based on data we have from another large population study that focuses on genetic data. We can then study molecules that are produced during the metabolic processes associated with these genes to see if they affect diet and risk of colorectal cancer.

All of this information will then be combined and investigated to see whether there is a causal relationship among them, using a technique that considers the natural distribution of genes in human populations.

Potential impact

This will be the largest study of its kind and will give a definitive answer on how diet increases or decreases the risk of colorectal cancer. The evidence will inform public health messages aimed at reducing the burden of colorectal cancer.

Grant publication

Bouras E, Kim AE, Lin Y, Morrison J, Du M, Albanes D, Barry EL, Baurley JW, Berndt SI, Bien SA, Bishop TD, Brenner H, Budiarto A, Burnett-Hartman A, Campbell PT, Carreras-Torres R, Casey G, Cenggoro TW, Chan AT, Chang-Claude J, Conti DV, Cotterchio M, Devall M, Diez-Obrero V, Dimou N, Drew DA, Figueiredo JC, Giles GG, Gruber SB, Gunter MJ, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Joshi AD, Kawaguchi ES, Keku TO, Kundaje A, Le Marchand L, Lewinger JP, Li L, Lynch BM, Mahesworo B, Männistö S, Moreno V, Murphy N, Newcomb PA, Obón-Santacana M, Ose J, Palmer JR, Papadimitriou N, Pardamean B, Pellatt AJ, Peoples AR, Platz EA, Potter JD, Qi L, Qu C, Rennert G, Ruiz-Narvaez E, Sakoda LC, Schmit SL, Shcherbina A, Stern MC, Su YR, Tangen CM, Thomas DC, Tian Y, Um CY, van Duijnhoven FJ, Van Guelpen B, Visvanathan K, Wang J, White E, Wolk A, Woods MO, Ulrich CM, Hsu L, Gauderman WJ, Peters U, Tsilidis KK. Genome-wide interaction analysis of folate for colorectal cancer risk. Am J Clin Nutr. 2023 Aug 26:S0002-9165(23)66108-8. doi: 10.1016/j.ajcnut.2023.08.010. Epub ahead of print. PMID: 37640106.