Genome-wide association study and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer

Scientists from the International Agency for Research on Cancer (IARC) and partner institutions reveal new findings about the lifestyle and genetic risk factors for early-onset colorectal cancer, which is colorectal cancer that is diagnosed in individuals younger than 50 years. The results were published in the Annals of Oncology.

The researchers first examined the genomes of more than 70 000 people, including almost 6200 patients with early-onset colorectal cancer, in the first dedicated genome-wide association study (GWAS) for the disease in young adults. They then conducted Mendelian randomization analyses to explore causal modifiable risk factors for the disease. The team were able to highlight the prominent role of pathways such as insulin signalling. They also identified probable causal associations of higher alcohol intake, higher body size parameters, higher fasting insulin levels, and lower educational attainment with greater risk of developing early-onset colorectal cancer.

The incidence of early-onset colorectal cancer is increasing globally, but the causes underlying this trend remain largely unknown. These results provide new insights into inherited susceptibility to early-onset colorectal cancer, including target genes and functional pathways, and reveal key modifiable targets for primary prevention, such as excess adiposity, hyperinsulinaemia, and alcohol consumption. These findings may help to prioritize individuals for personalized screening regimens or other intervention strategies.

Laskar RS, Qu C, Huyghe JR, Harrison T, Hayes RB, Cao Y, et al.
Genome-wide association study and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer
Ann Oncol, Published online 24 February 2024;
https://doi.org/10.1016/j.annonc.2024.02.008

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