Young-onset colorectal cancer risk among individuals with iron-deficiency anaemia and haematochezia

Objective Young-onset colorectal cancer (YCRC) incidence is rising. Scant data exist on YCRC risk after presentation with concerning symptoms such as iron-deficiency anaemia (IDA) or haematochezia. We examined the association between IDA and YCRC, and haematochezia and YCRC. Design Cohort study of US Veterans aged 18-49 years receiving Veterans Health Administration (VHA) care 1999-2016. IDA analytic cohort was created matching individuals without incident IDA to those with IDA 4:1 based on sex, birth year and first VHA visit date (n=239 000). We used this approach to also create a distinct haematochezia analytic cohort (n=653 740). Incident YCRC was ascertained via linkage to cancer registry and/or cause-specific mortality data. We computed cumulative incidence, risk difference (RD) and HRs using Cox models in each cohort. Results Five-year YCRC cumulative incidence was 0.45% among individuals with IDA versus 0.05% without IDA (RD: 0.39%, 95% CI: 0.33%-0.46%), corresponding to an HR of 10.81 (95% CI: 8.15-14.33). Comparing IDA versus no IDA, RD was 0.78% for men (95% CI: 0.64%-0.92%) and 0.08% for women (95% CI: 0.03%-0.13%), and RD increased by age from 0.14% for <30 years to 0.53% for 40-49 years. YCRC cumulative incidence was 0.33% among individuals with haematochezia versus 0.03% without haematochezia (RD: 0.30%, 95% CI: 0.26%-0.33%), corresponding to an HR of 10.66 (95% CI: 8.76-12.97). Comparing haematochezia versus no haematochezia, RD increased by age from 0.04% for <30 years to 0.43% for 40-49 years. Conclusion Colonoscopy should be strongly considered in adults aged <50 years with IDA or haematochezia without a clinically confirmed alternate source.