Risk of colorectal cancer after weight loss in the obese: a pooled cohort study.

Background: Though the link between obesity and colorectal cancer (CRC) is convincing, the impact of weight loss after obesity on CRC risk is unknown. Methods: This pooled study from the Multiethnic Cohort, Nurses' Health Study and Health Professionals Follow-Up Study included adults aged 45-75, with 3+ available body mass index (BMI) measures. The primary analysis included persons of all weights, with exposure (BMI) subjected to group-based trajectory modeling. Time-to-incident CRC was evaluated using accelerated failure time models. A subanalysis evaluated the risk of CRC in persons with obesity who had weight loss, compared to persons with stable obesity. Results: A total of 193,046 persons were analyzed (median age 49 years, 66% female). Among persons with severe degrees of obesity who lost weight, there was a longer CRC-free duration in whites (acceleration factor [AF] 2.30, 95% confidence interval [CI] 1.23-4.29; P=0.01), persons of "Other" race (AF 2.54, 95%CI 2.45-2.63; P<0.001), Asian/Native Hawaiian/Other Pacific Islanders (AF 1.11, 95%CI 1.06-1.18; P<0.001), and Black/African Americans (AF 1.09, 95%CI 1.07-1.10; P<0.001). BMI was not associated with altered CRC risk in Hispanic/Latinos. Among 40,606 persons with obesity who had weight loss, higher degrees of weight loss were associated with a longer CRC-free duration. While weight loss of 5-10% had an AF of 1.14 (95%CI 1.04-1.24; P=0.01), the optimal degree of weight loss was 15-20%, AF 1.53 (95%CI 1.28-1.83; P<0.001). Conclusions: Weight loss after obesity is associated with a lower CRC risk in diverse populations. In persons with obesity, 15-20% weight loss appears to be optimal.