Abstract 3735: A prospective study of excess weight and weight change in adulthood and risk of colorectal cancer incidence and mortality

Abstract Obesity is a rising public health problem in the U.S. and worldwide and excess body mass index (BMI, kg/m2) is a recognized risk factor for colorectal cancer (CRC). However, the role of weight change over the adult life course and timing of the excess BMI in relation to the incidence and mortality of CRC is not well understood. With >15 years of follow-up, we prospectively evaluated the risk of CRC incidence (n=3, 092) and mortality (n=931) in association with adult weight change among men and women (n=131, 814) recruited in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial at ages 55 to 74 between 1993 and 2001. At baseline, participants filled out a questionnaire reporting their weight and height at ages 20 years, 50 years, and baseline, allowing us to assess weight change from early to middle, middle to late, and early to late adulthood. Hazard ratios (HRs) and 95% confidence intervals (CI) were computed using multivariable-adjusted proportional hazard regression models. Higher BMI at all ages was associated with an increased risk of CRC incidence (p-trend=0.05, 0.0003 & 0.0001 for ages 20, 50 and baseline, respectively). Compared with individuals whose BMI never exceeded 25 kg/m2 over their lifetime, those who first exceeded a BMI of 25 kg/m2 in early adulthood had a slightly higher risk of CRC (HR=1.3, CI:1.1-1.4) than those whose BMI did not exceed 25 kg/m2 until middle age (HR=1.2, CI:1.1-1.3) or later (HR=1.2, CI: 1.0-1.3). Moreover, compared with stable weight, weight gain >4 kg per 5 years from early adulthood to middle or late adulthood was associated with an increased risk of CRC (HR=1.2, CI: 1.1-1.4 for both periods). The increased risks for weight gain >4 kg/5 years between early to middle adulthood appeared more pronounced for those with normal BMI at age 20 (HR=1.3, CI: 1.1-1.5). For CRC mortality, higher BMI at age 50 and baseline, but not age 20, was associated with increased risk (p-trend = 0.0002, 0.0002, and 0.3, respectively). Compared to those whose BMI never exceeded 25 kg/m2, those who first exceeded a BMI of 25 kg/m2 in early adulthood had an increased risk of mortality (HR=1.2, CI: 1.0-1.5), but no association was found for those whose BMI did not exceed 25 kg/m2 until middle adulthood or later. A higher risk of CRC mortality was observed for weight gain >4 kg/5 years from early adulthood to middle or late adulthood (HR=1.5, CI: 1.1-1.9 and HR=1.7, CI:1.4-2.1, respectively), especially among those with normal BMI at age 20 (HR=1.5, CI: 1.1-2.0 and HR=1.7, CI:1.3-2.2, respectively). Exceeding normal weight in early adulthood and weight gain from early to middle or late adulthood were associated with increased risks of both CRC incidence and mortality. These findings highlight the harms of excess BMI in early adulthood, the importance of maintaining healthy weight throughout the adulthood, and the potential benefit of weight control programs for CRC prevention. Citation Format: Wen-Yi Huang, Steven C. Moore, Kathryn Hughes Barry, Sonja I. Berndt. A prospective study of excess weight and weight change in adulthood and risk of colorectal cancer incidence and mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3735.