Evaluation Of Molecular Characteristics Of Early Onset Colorectal Cancer In A Population-Based Cohort Study

IntroductionThe reported increase in early onset colorectal cancer (EOCRC) incidence remains unexplained and is likely to be multifactorial. Understanding the molecular characteristics of EOCRC may give insights into aetiology, and inform potential treatment strategies that may be distinct from late onset disease. The aim of this analysis was to compare the molecular characteristics and survival of EOCRC with older colorectal cancer (CRC) patients in a population-representative cohort.MethodsClinicopathological data from 661 patients with Stage II or III colon adenocarcinoma diagnosed between 2004 and 2008 in Northern Ireland were analysed. Tissue blocks were retrieved, DNA extracted and microsatellite instability (MSI) and targeted gene mutation status ascertained. Chi-squared tests were used to compare molecular characteristics of EOCRC (<50 years old) versus older age groups (50–59, 60–69, 70–79 and ≥80 years old). Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (CI) for survival outcomes.ResultsEOCRC represented 5.8% of all Stage II and III colon cancer patients in this cohort. EOCRC patients did not have any BRAF or NRAS-mutant tumours, which was significantly different from older patients (p=0.004 and p=0.009, respectively). EOCRC tumours were more likely to have PIK3CA mutations compared to older patients (23.7% versus 15.6–19.7% in patients aged over 50 years old), and be MSI-high (33.3% versus 13.6–25.9% in patients aged over 50 years old), but these differences were not statistically significant. Compared to CRC patients aged 50–60 years old, EOCRC did not have a significantly increased risk of CRC specific death (adjusted HR 1.33; 95%CI 0.62–2.87).ConclusionsThis population-representative study found that EOCRC patients had no BRAF or NRAS-mutant tumours. PIK3CA-mutant and MSI-high tumours were overrepresented in EOCRC patients but this was not statistically significant. EOCRC patients were not at an increased risk of death, however further research in larger cohorts is required to investigate if differences in molecular characteristics, for example MSI status, may have implications for survival or novel adjuvant treatment strategies.