Adolescent to adulthood weight trajectories and the risk of obesity-related cancers, overall and early-onset: a population-based cohort study

Background High body mass index (BMI) is a modifiable cancer risk factor, projected to surpass smoking as the leading preventable risk factor. The impact of weight change from late adolescence to adulthood on cancer risk remains unclear. We aimed to assess the association between adolescence-to-adulthood BMI trajectories and obesity-related cancer risk. Methods A population-based cohort study of 800,024 people (45.1% women) insured by a large state-mandated health provider. BMI was measured during military pre-recruitment evaluations during 1967–2018 in adolescence and in subsequent clinic visits in adulthood during 1998–2020. Follow-up began one year after an adult BMI measurement until cancer diagnosis, death, transfer to another health provider, or December 16, 2021. BMI trajectories from adolescence to adulthood were classified as lean-to-lean, lean-to-high, high-to-lean, and high-to-high (cutoff: sex-specific and age-specific 85th percentile in adolescence, defined according to the United States Centers for Disease Control and Prevention growth charts, and 25 kg/m 2 in adulthood). Weight change was also assessed per 5% increments. The primary outcome was obesity-related cancers including esophagus, postmenopausal breast, liver and gallbladder, stomach, pancreas, colon and rectum, kidney, multiple myeloma, thyroid, uterus and ovary. The secondary outcome was obesity-related cancers diagnosed before age 50 years (early-onset cancers). Cox proportional hazards models were applied. Findings During 7,610,263 person-years, 6,376 people were diagnosed with obesity-related cancers, at a mean age of 53.3 ± 9.8 years. Adjusted hazard ratios (HRs) were 1.31 (95% confidence interval [CI], 1.24–1.39) for lean-to-high, 1.01 (95% CI, 0.78–1.31) for high-to-lean, and 1.47 (95% CI, 1.34–1.61) for high-to-high groups, compared to the lean-to-lean group. Respective HRs for early-onset obesity-related cancers were 1.33 (95% CI, 1.20–1.47), 0.88 (95% CI, 0.60–1.31), and 1.39 (95% CI, 1.20–1.61). Each 5% weight gain conferred a 3% increased hazard (95% CI, 1.02–1.03), with a similar 3% increase for early-onset cancers (95% CI, 1.02–1.04). Cancer-specific risks included 3% (95% CI, 1.02–1.04) for postmenopausal breast cancer, 3% (95% CI, 1.01–1.04) for colorectal cancer, 4% (95% CI, 1.02–1.05) for thyroid cancer, 5% (95% CI, 1.04–1.07) for kidney cancer, and 8% (95% CI, 1.06–1.09) for uterine cancer. Some cancers, including leukemia and non-Hodgkin's lymphoma, were not associated with weight gain but were positively associated with high adolescent BMI. Interpretation Maintaining a healthy BMI from adolescence to adulthood may reduce obesity-related cancer risk, including early-onset, highlighting the importance of early weight management strategies. Funding Novo Nordisk, Israel.