Distinct molecular profiles of sporadic early onset colorectal cancer: a population-based cohort and systematic review

Open AccessPublished:November 08, 2022DOI:
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      Background and aims

      The observed increase in incidence of early onset colorectal cancer (EOCRC) is being driven by sporadic cases, but the molecular characteristics of these tumours are not fully understood. Our objective was to investigate the prevalence of microsatellite instability (MSI) and selected mutations in sporadic EOCRC, and their association with survival.


      Firstly, we compared the prevalence of molecular characteristics and survival within a population-based cohort study of 652 Stage II and III colon cancer patients in Northern Ireland, comparing sporadic early onset (<50 years, n=35) with older (60-69 years, n=179) patients. Secondly, a systematic review for studies reporting the prevalence of MSI, mismatch repair deficiency (dMMR) or BRAF, KRAS, NRAS, PIK3CA and TP53 mutations in sporadic EOCRC was conducted. Meta-analysis was performed to calculate pooled estimates of the prevalence of molecular features in sporadic EOCRC.


      Firstly, within the cohort study, EOCRC patients did not have a significantly increased risk of CRC-specific death (adjusted HR 1.20; 95%CI 0.61-2.39) compared with 60-69 year olds. Secondly, 32 studies were included in the systematic review. Pooled analysis estimated a prevalence of 10% (95%CI 7-14%) for MSI-H/dMMR in sporadic EOCRC. BRAF and KRAS mutations had a prevalence of 1% (95%CI 0-3%) and 32% (95%CI 23-40%), respectively.


      The molecular characteristics of sporadic EOCRC differ from those of older adults, particularly regarding reduced prevalence of BRAF mutations. Ten percent of sporadic EOCRC display MSI-H/dMMR. Further studies are needed to address survival in sporadic EOCRC and whether molecular profiles influence EOCRC outcomes in this patient group.



      CIN (Chromosomal instability), CIMP (CpG Island methylator phenotype), CRC (Colorectal cancer), CI (Confidence intervals), dMMR (Deficient mismatch repair), EOCRC (Early onset colorectal cancer), ECOG (Eastern Cooperative Oncology Group), IBD (Inflammatory bowel disease), LOCRC (Late onset colorectal cancer), MSI-H (Microsatellite instability-high), MSS (Microsatellite stable), pMMR (Proficient mismatch repair)