BMI changes and presence of cofactors influence CRC risk in middle-aged and older Adults

Background: Effect modification by cofactors in the association between body mass index (BMI) change and colorectal cancer (CRC) risk has rarely been investigated. Methods: Cancer-free individuals who participated in the national health examinations and cancer screening at 2010 and underwent national health examination at 2014, were enrolled and followed through 2021 Results: Among 3.8 million, 42,555 patients developed CRCs. Persistent high BMI increased CRC risk comparing to persistent normal BMI. Among overweight individuals, BMI loss reduced CRC risk (adjusted hazard ratios [aHR] 0.93; 95 % confidence intervals [CIs] 0.88–0.99) and marked BMI gain (overweight to obesity II) increased CRC risk (aHR 1.91; 95 % CI 1.11–3.29). The impact of BMI change on CRC risk was significant across sex, age, and smoking status, with stronger effects in women, especially postmenopausal women. Persistent underweight in individuals over 50 years increased CRC risk (aHR 1.19; 95 % CI 1.05–1.34). Marked BMI gain increased CRC risk in men (normal to obesity I; aHR 1.21; 95 % CI 1.02–1.44) and women (overweight to obesity II; aHR 2.08; 95 % CI 1.16–3.74). Conclusions: These results highlight the hazardousness of persistent high BMI and further BMI gain with effect modification by cofactors.