Abstract 3034: Excess weight by degree and duration and cancer risk: an individual participant data (IPD) meta - analyses of over 1.4 million participants (ABACus2 consortium)
Authors: Hawwash Nadin , Sperrin Matthew , Martin Glen P. , Cook Michael , Matthews Charles E. , Neuhouser Marian L. , Joshu Corinne E. , Platz Elizabeth A. , Freisling Heinz , Gunter Marc , Bristow Rob , Renehan Andrew G. 
Published: April 2023

Abstract
Background: Excess body fatness, approximated by body mass index (BMI), is associated with higher risk of at least 13 cancer types and is the second-largest avoidable cause of cancer in many populations. Current epidemiologic evidence linking body fatness with cancer risk is largely based on a ‘once-only’ BMI measure which may fail to capture the life-course exposure to body fatness. Here, we test whether a novel metric that combines repeated BMI measures over an individual’s adult lifetime, the overweight-years metric, improves the performance characteristics for associations with cancer compared with a ‘once-only’ BMI measure.
Methods: Within the ABACus 2 Consortium (4 US cohorts; 1 European cohort), we derived the overweight-years metric - a product of the degree of overweight (BMI minus 24.9 kg/m2) and the duration of overweight (in years). Using a random effects two-stage meta-analysis, we calculated the association between the overweight-years metric, and separately the cumulative degree and cumulative duration of overweight exposure with incident cancer by fitting multivariable-adjusted Cox proportional hazards models and comparing each metrics performance with BMI measured at a single time using Harrell’s C-statistic.
Results: Out of 1,419,850 participants in the ABACus 2 consortium, 716,909 participants were included. Per standard deviation overweight-years, the multivariable-adjusted hazard ratio for obesity-related cancers in men was 1.15 (95% CI: 1.13, 1.17, I2: 0) and for women was 1.11 (95% CI: 1.04, 1.18, I2: 0.94). For ‘once-only’ BMI, the per standard deviation multivariable-adjusted hazard ratio for obesity-related cancers in men was 1.16 (95% CI: 1.15,1.18, I2: 0) and for women was 1.13 (95% CI: 1.09,1.18, I2: 0.82). For most obesity-related cancers, both degree and duration of overweight were significantly associated with risk. The overweight-years metric had a C-statistic of 0.610 (95% CI: 0.569, 0.649) and once-only BMI had a C-statistic of 0.608 (95% CI: 0.566, 0.648) for combined obesity-related cancers in men. In
women, the C-statistic for overweight-years was 0.562 (95% CI: 0.537, 0.587) and once-only BMI had a C-statistic of 0.566 (95% CI: 0.544, 0.588) for combined obesity-related cancers. The C-statistic of the overweight-years metric and BMI measured at a single time combined was 0.609 (95% CI: 0.567, 0.650) in men and 0.573 (95% CI: 0.546, 0.600) in women for combined obesity-related cancers.
Conclusion: Overall, there were marginal differences in the predictive performance between the overweight-years metric and a ‘once-only’ baseline-BMI measure. These findings show that excess weight throughout adulthood is important in cancer development.
Funding: CRUK, NIHR, NHLBI, NCI, NPCR.
Citation Format: Nadin Hawwash, Matthew Sperrin, Glen P. Martin, Michael Cook, Charles E. Matthews, Marian L. Neuhouser, Corinne E. Joshu, Elizabeth A. Platz, Heinz Freisling, Marc Gunter, Rob Bristow, Andrew G. Renehan. Excess weight by degree and duration and cancer risk: an individual participant data (IPD) meta - analyses of over 1.4 million participants (ABACus2 consortium) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3034.