Body Mass Index and Cancer Risk: The Evidence for Causal Association

Andrew G. Renehan*, 1, Matthias Egger2, Marcel Zwahlen2
1 Department of Surgery, School of Cancer, Enabling Sciences and Technology, University of Manchester, UK
2 Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland

© 2010 Renehan et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Surgery, University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX United Kingdom; Tel: +44 161 446 3157; Fax: +44 161 446 3365; E-mail:


Increased body mass index (BMI), as an approximation of body adiposity, is a risk factor for developing several adult malignancies. To quantify these risks, we reported a comprehensive systematic review (Lancet 2008; 371: 569-78) of prospective observational studies determining associations between BMI and risk of incident cancer for 20 cancer types. We demonstrated that associations are: (i) sex-specific; (ii) exist for a wider range of malignancies than previously thought; and (iii) are broadly consistent across geographic populations. In the present paper, we tested these data against the Bradford-Hill criteria of causal association, and argue that the available data support strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence and probably analogy. However, the experimental evidence supporting reversibility is currently lacking, though indirect evidence from longitudinal data in cohort studies and long-term follow-up post-bariatric surgery is emerging. We additionally assessed these data against appropriate adjustment for available confounding factors; measurement error and study design; and residual confounding; and found lack of alternative explanations. We conclude that there is considerable evidence to support a causal association between BMI and risk for many cancer types, but in order to establish the role of weight control in cancer prevention, there is a need to develop trial frameworks in which to better test reversibility.

Keywords: Body mass index, obesity, cancer risk, causal association.