Risk Factors for Early-Onset Colorectal Cancer: A Canadian Prospective Cohort Study

Purpose: The incidence of early-onset (<50 years of age) colorectal cancer (eoCRC) has been steadily increasing in high-income countries including Canada. Despite this increase in incidence, the etiology of eoCRC remains unclear and prospective cohort studies of potential risk factors are limited. Methods: We examined two prospective cohorts of healthy individuals (<50 years of age) who completed baseline questionnaires in the Ontario Health Study and Alberta's Tomorrow Project. We examined the associations between demographic characteristics, chronic health conditions, and lifestyle behaviours with the development of eoCRC using Cox proportional hazard models. Cohorts were analyzed separately and hazard ratios for each risk factor were pooled with random effects meta-analyses. Results: During an average follow-up of 6.63 years, 98 eoCRC cases occurred among study participants (n=127,852). A family history of CRC alone or with a history of other cancer types was associated with an increased risk of developing eoCRC (HR: 2.76, 95% CI: 1.43-5.32), but a family history of a non-CRC cancer only was not (HR: 1.18, 95% CI: 0.61-2.30). Heavy smokers (>= 10 pack-years) at baseline had a higher risk of eoCRC compared to non-smokers (HR: 1.87, 95% CI: 1.00-3.52). Sex, socioeconomic factors, diabetes, alcohol consumption, among other factors were not significantly associated with the risk of eoCRC. Conclusion: Our findings indicate that specific CRC risk factors are also associated with developing eoCRC. The data in the study offers valuable insights that could be integrated in future meta-analyses. Additional prospective cohort studies are required to understand the etiology of eoCRC.