A sweeping analysis of 1.5m cancer cases shows that excess body weight may shape cancer risk more broadly than previously recognised, with risks varying by cancer type, sex, and region, say global researchers.
In their recent systematic review and meta-analysis published in Nature Metabolism, they synthesised decades of peer-reviewed literature to re-evaluate the global relationship between body mass index (BMI) and cancer risk, reports News Medical.
The analyses pooled data from more than 1.5m documented cancer cases and found that an elevated BMI is positively linked to 19 distinct cancer types, substantially more than the 13 previously recognised by consensus reports.
The review further identified notable regional and sex-based variations in these risks and found that genetic evidence generally supported many of the observational associations, although not uniformly across all cancer types.
Background
The association between excessive body weight and cancer risk is by no means a novel concept. For years, major health organisations like the World Cancer Research Fund (WCRF) and the International Agency for Research on Cancer (IARC) have warned that carrying excess weight increases the risk of developing at least 13 types of cancer.
However, as global obesity rates continue to demonstrate unprecedented growth, particularly in low- and middle-income countries, researchers emphasise significant gaps in our understanding of how these factors operate biologically.
For example, it remains unclear whether obesity-related cancer risks apply equally across different global populations or if alternative metrics, like waist circumference, offer a clearer picture of the association between adiposity and subsequent cancer risk.
While previous reviews have aimed to address these knowledge gaps, they lacked data from diverse geographic regions (most focused on American and European populations) and did not include data from next-generation genetic cohorts, thereby necessitating a re-evaluation of the variables that best explain these observational relationships.
About the review
The present review aimed to meet these requirements and inform future weight management and oncological policy by comprehensively synthesising prospective cohort studies from online scientific repositories (PubMed, EMBASE, and Scopus) from database inception to April 2025.
The review’s final publication set comprised 226 distinct peer-reviewed articles (n = 1 520 512 incident cancer cases) spanning data from 23 countries (six major geographical locations) and capturing an unprecedented 557 separate BMI-cancer risk associations across 25 common cancer types.
For the meta-analyses, all risk ratios from included publications were standardised to a scale measuring a 5 kg/m² increase in BMI, thereby maintaining statistical uniformity and enabling direct comparisons between previously non-overlapping datasets.
Since most of the datasets were observational (identifying correlations), Mendelian randomisation (MR) analyses were used to strengthen causal inference. MR analyses use inherited genetic variants as proxies for lifelong exposure to the variable under investigation (herein, elevated body weight).
Finally, to minimise the impacts of tobacco use (as a residual confounder), smoking-related cancers were evaluated using data from lifelong never-smokers.
Study findings
The meta-analyses revealed statistically significant evidence linking higher participant BMI to an elevated risk of 19 distinct cancer types, with risk estimates varying nearly 20-fold in magnitude across cancer types.
For example, at the highest extreme, the analyses showed that every 5-unit increase in BMI was associated with a 58% increase in endometrial cancer risk (relative risk [RR] = 1.58, 95% confidence interval [CI]: 1.51–1.67) and a 47% increase in oesophageal adenocarcinoma risk (RR = 1.47).
Most importantly, the data uncovered positive links for leukaemia (RR = 1.09), non-Hodgkin lymphoma (RR = 1.05), bladder cancer (RR = 1.04), and glioma (RR = 1.03), none of which has been previously recognised as malignancies associated with excessive BMI in previous consensus statements.
The authors also reported inverse associations for premenopausal breast cancer, lung cancer among never-smokers, and oesophageal squamous cell carcinoma among never-smokers.
The study further identified significant regional disparities in the observed associations between BMI and cancer risk. For instance, postmenopausal breast cancer risks tied to a 5-unit BMI increase were found to show roughly double the excess relative risk in East Asian cohorts (RR = 1.25) compared with their European counterparts (RR = 1.11, p-heterogeneity = 7.6 × 10−6), highlighting the non-generalisability of results from the latter cohort on the former.
Similarly, sex-based differences were identified, as illustrated in colorectal cancer associations, which were substantially stronger in men (RR = 1.17) than in women (RR = 1.06, p-heterogeneity = 8.9 × 10−¹0). In contrast, the BMI-gallbladder cancer association was stronger in women (RR = 1.33) than in men (RR = 1.13, p-heterogeneity = 9.5 × 10−5).
Finally, when comparing BMI versus waist circumference as predictors of subsequent cancer risk, the review found that both variables yielded broadly similar risk estimates, although modest differences were observed for some cancer types.
Conclusions
The present review validates previous research indicating the substantial impact of obesity on cancer risk and global cancer burden, while highlighting that past frameworks heavily under-represented regional risks, particularly in East Asian populations, where differences in hormone therapy use, oestrogen exposure, gallstone aetiology, tumour subtype patterns, surveillance, or residual confounding may partly explain variation in susceptibility.
Furthermore, the review underscores that major regional limitations persist, with Africa, South Asia, and Central America (among other regions) remaining under-represented by long-term cancer incidence cohorts even in the present study.
Future research should prioritise diverse, understudied populations to help elucidate a truly equitable understanding of modifiable cancer risk factors.
Study details
Adiposity and cancer: systematic review and meta-analysis
Eleanor L. Watts, Amparo Gonzalez-Feliciano, Marc Gunter, Nilanjan Chatterjee & Steven C. Moore.
Published in Nature Metabolism on 15 June 2026
Abstract
Obesity is a major health challenge. Here we show that body mass index is positively associated with risk of 19 cancers and inversely associated with 3, based on a systematic review and meta-analysis of prospective studies of 25 cancer types. We searched PubMed, EMBASE and Scopus through to 23 April 2025, identifying 226 articles comprising 1.5 million incident cancers. We identified positive associations for leukaemia, non-Hodgkin lymphoma, bladder cancer and glioma, not previously identified by major consensus reports. Associations differed according to region and sex, with stronger associations for postmenopausal breast and ovarian cancers in East Asia, weaker associations for gallbladder cancer in East Asia and in men, and stronger associations for colorectal cancer in men. Body mass index and waist circumference showed similar associations with cancer. We reviewed Mendelian randomisation and imaging-based studies; genetic findings were generally consistent with observational associations, while imaging data were limited. Our findings underscore the impact of obesity on cancer risk.
Nature Metabolism article – Adiposity and cancer: systematic review and meta-analysis (Open access)
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Significant link between high BMI and certain cancers
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