Jinming Li, Yedong Pan, Fanying Guo. Lancet Oncol.. 2025 Aug;26(8):1055-1066
The increasing incidence of early-onset colorectal cancer (age <50 years; EOCRC) shows a dramatic growing trend globally, while late-onset colorectal cancer (LOCRC) is gradually decreasing. Between Jan 1 and Dec 31, 2024, 17 133 tumor samples from patients with colorectal cancer in eight countries were analyzed. In hypermutated colorectal cancer, EOCRC exhibited a significantly higher TMB compared with LOCRC (p<0·0001). In non-hypermutated colorectal cancer, EOCRC showed a significantly lower TMB than LOCRC after adjusting for skewness (p<0·0001). In hypermutated colorectal cancer, a total of 23 genes, including APC, KRAS, CTNNB1, and TCF7L2 displayed elevated mutation frequencies in EOCRC compared with LOCRC. In non-hypermutated colorectal cancer, only TP53 showed a higher mutation frequency in EOCRC. Within hypermutated colorectal cancer, younger patients exhibited a higher mutational burden than older patients. Our study reveals an abnormal accumulation of distinct somatic mutations in hypermutated EOCRC, the pattern of which might be contributing to the alarming rise in the incidence of EOCRC over the past decades. Our results support the need for EOCRC-specific molecular profiling to guide clinical practice.
24 Mar, 2026