Whether body mass index (BMI) is causally associated with the risk of being diagnosed with or dying from any cancer remains unclear. Weight reduction has clinical importance for cancer control only if weight gain causes cancer development or death. We aimed to answer the question 'does genetically predicted BMI influence my risk of being diagnosed with or dying from any cancer'.
We used a Mendelian randomisation (MR) approach to estimate causal effect of BMI in 46,155 white-British participants aged between 40 and 69 years at recruitment (median age at follow-up 61 years) from the UK Biobank, who developed any type of cancer, among whom 6998 died from cancer. To derive MR instruments for BMI, we selected up to 390,628 cancer-free participants.
For each standard deviation (4.78 units) increase in genetically predicted BMI, we estimated a causal odds ratio (COR) of 1.07 (1.02–1.12) and 1.28 (1.16–1.41) for overall cancer risk and mortality, respectively. The corresponding estimates were similar for males and females, and smokers and non-smokers.
Higher genetically predicted BMI increases the risk of being diagnosed with or dying from any cancer. These data suggest that increased overall weight may causally increase overall cancer incidence and mortality among Europeans.
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This work was conducted using the UK Biobank Resource (application number 25331). We thank Scott Wood and John Pearson from QIMR Berghofer for IT support. This work was supported by a project grant [grant number 1123248] from the Australian National Health and Medical Research Council (NHMRC). J.-S.O. received scholarship support from the University of Queensland and QIMR Berghofer Medical Research Institute. S.M. was supported by a fellowship from the Australian Research Council. D.C.W., S.M. and R.E.N. are supported by research fellowships from the Australian National Health and Medical Research Council (NHMRC). The study funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
S.M., R.E.N., P.G., M.H.L., and D.C.W. were involved in conceptualisation and funding acquisition. J.-S.O., J.A., P.G., M.H.L., and S.M. were involved in formal analysis. P.G., J.-S.O., and S.M. participated in the original draft preparation. All authors contributed to the review and editing of the final version of the paper. P.G. and J.-S.O. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
The authors declare no competing interests.
The study was approved by the National Research Ethics Service Committee North West—Haydock, and all study procedures were performed in accordance with the World Medical Association Declaration of Helsinki ethical principles for medical research.
All participants provided informed written consent.
The UK Biobank data are available through the UK Biobank Access Management System (http://www.ukbiobank.ac.uk/).
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