Conflicting Relationship Between Obesity and Cancer Risk

Dawn O'Shea

September 01, 2021

Higher adiposity may increase the risk of non-hormonal cancer but lower the risk of some hormone-related cancers, according to an analysis of participants in the UK biobank.

While observational and Mendelian randomisation (MR) studies suggest a link between obesity and cancer, it remains unclear if these associations are dependent on related metabolic abnormalities.

A study published in the  International Journal of Obesity  used data from 321,472 biobank participants, which included 30,561 cases of obesity-related cancer. Three genetic instruments were developed which reflected higher adiposity together with either unfavourable (82 single nucleotide polymorphisms [SNPs]), favourable (25 SNPs) or neutral (24 SNPs) metabolic profile to examine the association with 14 types of cancer, previously thought to be associated with obesity.

All genetic instruments had a strong association with body mass index. The instrument reflecting unfavourable adiposity was also associated with higher C-reactive protein, HbA1c and adverse lipid profile, whereas the instrument reflecting metabolically favourable adiposity was associated with lower HbA1c and a favourable lipid profile.

In MR-inverse-variance weighted analysis, unfavourable adiposity was associated with an increased risk of non-hormonal cancers (OR, 1.22; 95% CI, 1.08-1.38) but a lower risk of hormonal cancers (OR, 0.80; 95% CI, 0.72-0.89).

Analyses suggested causal increases in the risk of multiple myeloma (OR, 1.36; 95% CI, 1.09- 1.70) and endometrial cancer (OR, 1.77; 95% CI, 1.16-2.68) with unfavourable adiposity but lower risks of breast (OR, 0.72; 95% CI, 0.61-0.83) and prostate cancer (OR, 0.81; 95% CI, 0.68-0.97).

These findings conflict with observational studies which have reported that obesity is associated with an increased risk of prostate and postmenopausal breast cancer. The authors suggest that the discrepancy between observational and MR studies may be related to the genetic instruments used in this study which reflect subtle life-long exposure to adiposity rather than current levels of adiposity or obesity.

Favourable or neutral adiposity were not associated with the odds of any individual cancer.

The findings suggest that the presence of metabolic abnormalities might aggravate the adverse effects of higher adiposity on cancer. The authors said it is possible that genetically predicted adiposity may better capture differences at the key stages of hormonal development, and thereby, have a differing effect on hormone-dependent cancers compared with adult obesity.

They said further studies are warranted to investigate whether interventions on adverse metabolic health may help to alleviate obesity-related cancer risk.


Ahmed M, Mulugeta A, Lee SH, Mäkinen VP, Boyle T, Hyppönen E. Adiposity and cancer: a Mendelian randomization analysis in the UK biobank. Int J Obes (Lond). 2021 Aug 27 [Epub ahead of print]. doi: 10.1038/s41366-021-00942-y. PMID: 34453097

This article originally appeared on Univadis, part of the Medscape Professional Network.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: