High BMI increases risk of 19 types of cancer, as global review expands link between obesity and cancer.

A comprehensive analysis of 1.5 million cancer cases shows that excess body weight may pose a broader cancer risk than previously recognized, with risks varying by cancer type, gender and region.

He studies: Obesity and cancer: systematic review and meta-analysis. Image credit: Piyawat Nandinuparit/Shutterstock

In a recent systematic review and meta-analysis published in the journal Normal metabolismresearchers pooled decades of peer-reviewed literature to re-evaluate the global relationship between BMI (Body mass index) and cancer risks.

The analyzes combined data from more than 1.5 million documented cancer cases and found that a high BMI was positively associated with 19 different types of cancer, far more than the 13 types previously identified through pooled reports. The review also identified notable regional and sex differences in these risks, and found that genetic evidence generally supports several observational associations, although it is not uniform across all cancers.

AA total of 25 types of cancer. forIndividual cancers. Estimates from pooled studies covering multiple regions for which country-specific case numbers were not available were excluded from this figure (head and neck). Numbers may not add due to rounding.

background

The relationship between excess body weight and cancer risk is by no means a new concept. For many years, major health organizations such as the World Cancer Research Fund (WCRF(and the International Agency for Research on Cancer)International Agency for Research on CancerThey warned that carrying excess weight increases the risk of at least 13 types of cancer.

However, as global obesity rates continue to show unprecedented growth, especially in low- and middle-income countries, researchers emphasize that there are significant gaps in our understanding of how these factors work biologically.

For example, it remains unclear whether the cancer risks associated with obesity apply equally to different global population groups or if alternative measures, such as waist circumference, provide a clearer picture of the association between obesity and subsequent cancer risk.

While previous reviews aimed to address these knowledge gaps, they lacked data from diverse geographic regions (mostly focused on American and European populations) and did not include data from next-generation genetic cohorts, necessitating a re-evaluation of the variables that best explain these observational relationships.

About the review

The present review aims to meet these requirements and inform future weight management and oncology policy through comprehensive synthesis of prospective cohort studies from online scientific repositories (PubMed, EMBASE, Scopus) from database inception until April 2025.

The review’s final publication pool consisted of 226 distinct peer-reviewed articles (n=1,520,512 cancer cases) covering data from 23 countries (6 major geographic locations) and capturing an unprecedented 557 separate associations of BMI cancer risk across 25 common cancer types.

For the meta-analyses, all risk ratios from included publications were standardized to a scale measuring a 5 kg/m increase in BMI, thus maintaining statistical uniformity and enabling direct comparisons between previously non-overlapping data sets.

Since most data sets were observational (identifying associations), Mendelian randomization was done (Mr.) Analyzes were used to strengthen causal inference. MR analyzes use inherited genetic variants as proxies for lifetime exposure to the variant under investigation (here, high body weight).

Finally, to reduce the effects of tobacco use (as a remaining confounding factor), smoking-related cancers were assessed using data from people who had never smoked in their lifetime.

Study results

Meta-analyses revealed statistically significant evidence linking participants’ higher BMI and higher risk of 19 different types of cancer, with risk estimates varying by about 20 orders of magnitude across cancer types. For example, at the highest end, analyzes showed that every 5-unit increase in BMI was associated with a 58% increase in the risk of developing endometrial cancer (relative risk [RR] = 1.58, 95% confidence interval [CI]: 1.51-1.67) and a 47% increase in the risk of developing esophageal adenocarcinoma (RR = 1.47).

Importantly, the data revealed positive associations for leukemia (RR = 1.09), non-Hodgkin lymphoma (RR = 1.05), bladder cancer (RR = 1.04), and glioma (RR = 1.03), none of which were previously recognized as malignancies associated with excessive BMI in previous consensus data.

Researchers also reported inverse associations with premenopausal breast cancer, lung cancer among never smokers, and esophageal squamous cell carcinoma among never smokers.

The study also identified large regional variations in the observed associations between BMI and cancer risk. For example, postmenopausal breast cancer risks associated with a BMI increase of 5 units have been shown to exhibit approximately twice the excess relative risk in East Asian groups (RR = 1.25) compared to their European counterparts (RR = 1.11, heterogeneity = 7.6 × 10 ).^-6), highlighting the lack of generalizability of results from the latter group to the former.

Likewise, sex-based differences were identified, as shown by associations with colorectal cancer, which were significantly stronger in men (RR = 1.17) than in women (RR = 1.06, heterogeneity = 8.9 × 10^–¹⁰). In contrast, the association between BMI and gallbladder cancer was stronger in women (RR = 1.33) than in men (RR = 1.13, heterogeneity = 9.5 × 10).^-5).

Finally, when comparing BMI versus waist circumference as predictors of later cancer risk, the review found that both variables yielded broadly similar risk estimates, although modest differences were observed for some cancers.

Conclusions

The present review validates previous research indicating the significant impact of obesity on cancer risk and global cancer burden, highlighting that previous frameworks have under-represented regional risks, particularly in East Asian populations, where differences in use of hormone therapy, estrogen exposure, etiology of gallstones, patterns of tumor subtypes, surveillance, or residual confounders may partly explain variation in susceptibility.

Furthermore, the review emphasizes that major regional limitations remain, with Africa, South Asia and Central America (among other regions) remaining underrepresented by long-term cancer incidence groups even in this study.

Future research should prioritize diverse, understudied populations to help elucidate a truly equitable understanding of modifiable cancer risk factors.

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