Sensitive Period Analysis of Adulthood BMI and Cancer Risk: An Individual Participant Data Meta-Analysis of Over 720,000 Participants in the ABACus 2 Consortium

At least 13 cancers are linked to obesity. We analyse time-to-event data using Sensitive Period Analysis to explore whether associations between body mass index (BMI) and cancer incidence vary throughout adulthood to inform cancer prevention strategies, policy and weight management trials of optimal intervention ages. Using the European Prospective Investigation into Cancer and Nutrition cohort, Atherosclerosis Risk in Communities study, Women's Health Initiative, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial, NIH-AARP Diet and Health, we predicted BMI throughout adulthood. We landmarked to predefined ages of interest (AOI), ages 30 to 65 (5-yearly). Super-landmarking and a two-stage IPD meta-analysis were used. A single stratified Cox proportional hazards model with interaction terms between BMI and AOIs was fitted to analyse associations between per 5 kg/m² BMI at AOIs and cancer incidence and identify sensitive age periods. 720,210 participants were followed up over 9.85 years in men and 10.80 years in women. Positive associations were found per 5 kg/m² BMI across ages 30–65 for obesity-related cancers. Some evidence suggests BMI in the 40s–50s raises cancer risk more than baseline. Interactions by age were found in women at ages 35 and 40 for obesity-related cancers with HRs per 5 kg/m² of 1.04 (95% CI: 1.01, 1.07, I²:0%) and 1.05 (95% CI: 1.01, 1.09, I²:50%), respectively, and at ages 35–65 for postmenopausal breast cancer. Higher BMI increased obesity-related cancer risk across ages 30–65. Similar associations across adulthood suggest adiposity at any age increases cancer risk. Policymakers should prevent excess adiposity accumulation in early life to minimise cancer risk.