Associations of Whole and Refined Grain Intake with Colorectal Cancer Risk: Dose–Response and Isocaloric Substitution Analyses in a Multi-Center Population-Based Case–Control Study

The associations between dietary factors, whole and refined grains, and colorectal cancer (CRC) remain unclear, particularly in Middle Eastern populations. This multicenter, population-based case-control study assessed the associations between whole and refined grain intake and CRC risk in adults across three provinces in Iran. A total of 402 CRC patients and 825 controls were included. CRC was confirmed by colonoscopy, and dietary intake was assessed using a validated food-frequency questionnaire. Individuals in the highest tertile of whole-grain consumption had a 52% lower risk of CRC compared with those in the lowest tertile (OR: 0.48; 95% CI: 0.32-0.74), whereas individuals in the highest tertile of refined grain intake had 2.62 times higher odds of CRC (OR: 2.62; 95% CI: 1.62-4.24). Dose-response analyses indicated a non-linear inverse association for whole grains, with the greatest risk reduction observed between 50 and 100 g/day. Substitution analyses showed that replacing refined grains with whole grains was associated with a modest reduction in CRC risk (OR: 0.91; 95% CI: 0.85-0.97). These findings suggest that higher whole-grain intake significantly reduces CRC risk, whereas refined-grain consumption substantially increases it, supporting dietary strategies that promote whole-grain intake for CRC prevention.