Abstract 3632: Adiposity and cancer: Updated meta-analysis incorporating the largest evidence base to date

Abstract Background: Global increases in body mass index (BMI) have made obesity a major public health challenge worldwide. Between 2016 and 2018, landmark reviews by the WCRF and IARC established elevated BMI as a risk factor for at least 12 cancers, yet uncertainties remain regarding generalizability beyond Europe and North America, associations with less common or smoking-related cancers, and the relevance of other adiposity measures such as waist circumference. Since these reviews, new large-scale cohorts, particularly in East Asia, and Mendelian randomization studies have greatly expanded available evidence, enabling reassessment of obesity-cancer associations. Methods: We conducted a systematic review and meta-analysis of prospective cohorts examining BMI and risk of 25 common cancers, searching PubMed, EMBASE, and Scopus through April 23, 2025. Summary risk estimates were calculated using random-effects meta-analysis. We also meta-analysed Mendelian randomization studies, compared associations for BMI and waist circumference, and reviewed emerging imaging-based evidence. Results: Across 226 articles comprising 1.5 million cancer data points, most cases originated from Europe (59.0%), followed by East Asia (30.1%) and North America (10.6%). BMI was positively associated with 19 cancer types and inversely associated with three. Positive associations for leukaemia (RR per 5 kg/m2 = 1.09, 95% CI 1.05-1.13), non-Hodgkin lymphoma (1.05, 1.01-1.08), bladder cancer among never-smokers (1.04, 1.01-1.07), and glioma (1.03, 1.01-1.05) represent novel findings not reported in previous WCRF or IARC reviews, suggesting obesity may be linked to a broader range of cancers than previously recognised. For cancers where smoking is a dominant risk factor, we observed increased risks for head and neck cancer (1.07, 1.02-1.13) and bladder cancer, and decreased risks for oesophageal squamous cell carcinoma (0.72, 0.60-0.86) and lung cancer (0.92, 0.86-0.99) among never-smokers. Regional variation was evident, including stronger associations for postmenopausal breast and ovarian cancers in East Asia and weaker associations for gallbladder cancer, although many populations remain unrepresented. Mendelian randomization analyses were broadly consistent with a causal effect. Associations for BMI and waist circumference were highly similar, and available imaging data were limited. Conclusions: This updated meta-analysis, representing the largest synthesis of evidence to date, highlights the substantial and expanding impact of obesity on cancer risk and underscores the urgent need to address this modifiable risk factor worldwide. Citation Format: Eleanor Watts, Amparo Gonzalez-Feliciano, Marc Gunter, Nilanjan Chatterjee, Steven Moore. Adiposity and cancer: Updated meta-analysis incorporating the largest evidence base to date [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3632.