28. 03. 2024
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In the highly impacted and prestigious journal Annals of Oncology (open in a new window) (IF 50,5), a new international study will soon be published, co-authored by geneticist Pavel Vodička – head of the Department of Molecular Biology of Cancer.
The incidence of early colorectal cancer EOCRC is increasing worldwide, but the reasons for this unfavourable trend are largely unclear. However, it is known that a number of important genetic and environmental factors are involved in the development of this serious disease. In a study entitled „Genome-wide association study and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer (otevře se v novém okně)“, , researchers conducted the first genome-wide association study (GWAS) and Mendelian randomisation analysis (MR) specific to EOCRC to investigate germline genetic and causally modifiable risk factors associated with the development of colorectal cancer in young people.
Scientists conducted a genome-wide association study meta-analysis of 6176 EOCRC cases and 65829 controls from the following consortiums: GECCO, CORRECT, CCFR, and UK Biobank. They found two novel risk loci for EOCRC, not previously associated with CRC risk, and identified a deleterious coding variant in polyposis-associated DNA repair gene MUTYH. The scientists also identified new EOCRC susceptibility genes, and in addition to pathways such as TGFβ, SMAD, BMP, and PI3K signalling, our study highlights the role of insulin signalling and immune/infection-related pathways in EOCRC. In addition to genetic variants, they found novel evidence of probable causal associations for higher levels of body size and metabolic factors – such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, fasting insulin, and higher alcohol consumption, with increased EOCRC risk.
The new study not only highlights hereditary susceptibility to EOCRC but also suggests preventive and screening lifestyle goals.