Obesity is a major public health concern affecting 1 billion adults and children worldwide.1 In parallel, there is a growing burden of cancer globally; in 2020 more than 19 million people were diagnosed with cancer, and this figure is projected to increase to more than 30 million new cases per year by 2040.2 Obesity is now recognised as an important cause of some cancers. Based on a 2016 evaluation by the International Agency for Research on Cancer (IARC), obesity was established as a cause of cancers of the breast (postmenopausal), colorectum, endometrium, ovary, kidney, liver, gallbladder, gastric cardia, oesophagus (adenocarcinoma), thyroid and pancreas as well as for multiple myeloma and meningioma.3,4 Given the rising prevalence of obesity, it is possible that the incidence of obesity-related cancers will continue to increase in the coming decades.
In the October issue of the Lancet Regional Health Europe, Sun et al. report findings from a large-scale multi-cohort analysis in Sweden that examined the association of body mass index (BMI) with cancer risk.5 With a sample size of more than 4 million individuals and ∼332,000 incident cancer diagnoses, as well as height and weight measured in their 20s for the majority of participants, the study is unprecedented in its ability to explore associations between obesity and cancers including rare tumours and sub-types. Of the 122 cancer types examined, the analysis identified 18 tumour types that are not currently recognised as obesity-related cancers, adding to the 13 already established by the IARC evaluation (Table 1). The relative risks for the association of BMI with the newly identified obesity-related cancers were 1.17 (95% confidence interval, 1.15–1.20) per 5 kg/m2 in men and 1.13 (95% confidence interval, 1.11–1.15) in women—magnitudes broadly consistent with cancers with an already established link with obesity. These newly-identified obesity-related cancers include those with strong links to smoking and for which prior evidence for associations with obesity were inconsistent such as head and neck cancers; haematological malignancies such as B-cell lymphoma, which had been judged as potentially related to obesity but for which there was prior insufficient evidence; as well as small intestinal cancer, malignant melanoma, and cancers of the genital and endocrine organs, and connective tissue. While previous research had linked obesity to some of these cancers, the current study enabled analyses of these rarer cancers with greater precision and provides more robust evidence on their potential relationship with obesity.
Table 1.
Established obesity-related cancers and potential obesity-related cancers based on Sun et al.
| Established obesity-related cancersa | Potential obesity-related cancersb |
|---|---|
| Breast (post-menopausal) | Cervix (adenocarcinoma) |
| Endometrium | Vulva |
| Ovary | Penis |
| Colorectum | Gastric (gastrointestinal stromal tumours) |
| Gallbladder | Biliary Tract |
| Gastric cardia | Pancreatic islets |
| Liver | Small intestine |
| Oesophagus (adenocarcinoma) | |
| Pancreas | Parathyroid gland |
| Kidney | Pituitary gland |
| Thyroid | Adrenal gland |
| Connective Tissue | |
| Meningioma | Lymphoid Neoplasms |
| Myeloid Neoplasms | |
| Multiple Myeloma | Oral cavity |
| Nasal and Paranasal Sinuses | |
| Head and Neck (adenocarcinoma) | |
| Head and Neck (squamous cell carcinoma) | |
| Malignant Melanoma | |
| Nodular Melanoma |
Despite these strengths, the study has some limitations which are important to consider when interpreting the findings. For example, the majority of participants lacked information on smoking which is potentially an influential confounding variable in the association of obesity with cancer. However, in a sub-analysis among ∼800,000 participants with available data on smoking the associations were generally directionally consistent as those in the full analysis. Other important potential confounders such as reproductive factors and information on prior infections were also missing on most participants. The e-value sensitivity analyses suggest that the associations are unlikely to be entirely explained by confounding, but lack of adjustment for confounders other than smoking means that the magnitude of the risks for these additional cancer sites remain uncertain.
As the current study demonstrates, the pooling of data across large-scale cohorts offers opportunities to examine obesity as a risk factor for numerous cancer types and as cohort resources continue to grow the compendium of cancers linked to obesity may expand further. The results of this study also now raise the question of whether obesity could be considered a “universal carcinogen” if it can cause cancer in most tissues at all ages although with differences in magnitude due to tissue specificity and susceptibility. In this regard, it is tempting to draw parallels with ionizing radiation, which after more than 100 years of epidemiological studies has been found to cause cancer in most tissues. With longer follow-up and larger study populations there are now only a few cancer types that appear not to be radiation-inducible.6
How obesity causes cancer is subject to some debate and the precise mechanistic underpinnings are not fully delineated. Certainly, obesity exhibits several of the key characteristics of carcinogens including induction of chronic inflammation and oxidative stress as well as altering cell proliferation, cell death and nutrient supply.7 It is plausible that these systemic mechanisms could influence a wide range of cells and tissue types thus supporting the notion that obesity may be a universal carcinogen. In Sun et al., obesity-related cancers accounted for 25% of all cancers but this increased to 40% with the addition of these new potentially-obesity related tumour types. Therefore, public health measures aimed at reducing obesity either through behaviour, surgery or pharmacological means could potentially prevent multiple cancers. Further research in this area is needed to identify causal pathways and targets for cancer interception among susceptible individuals.
Contributors
Writing and Reviewing (M.J. G and A.BdG).
Declaration of interests
None (M.J.G and A.BdG).
References
- 1.NCD Risk Factor Collaboration (NCD-RisC) General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7.5 million participants. Lancet. 2024;404(10455):851–863. doi: 10.1016/S0140-6736(24)01405-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Cancer tomorrow [website] International Agency for Research on Cancer; Lyon: 2020. https://gco.iarc.fr/tomorrow/en [Google Scholar]
- 3.Lauby-Secretan B., Scoccianti C., Loomis D., Grosse Y., Bianchini F., Straif K. Body fatness and cancer: viewpoint of the IARC working group. N Engl J Med. 2016;375(8):794–798. doi: 10.1056/NEJMsr1606602. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.vol 16. World Health Organization; Geneva: 2016. IARC handbooks of cancer prevention. (Body fatness). https://www.iarc.who.int/featured-news/media-centre-iarchandbooks16. [Google Scholar]
- 5.Sun M., da Silva M., Bjørge T., et al. Body mass index and risk of over 100 cancer forms and subtypes in 4.1 million individuals in Sweden: the Obesity and Disease Development Sweden (ODDS) pooled cohort study. Lancet Reg Health Eur. 2024;45 doi: 10.1016/j.lanepe.2024.101034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Berrington de Gonzalez A., Bouville A., Rajaraman P., Schubaeur-Berigan M. In: Schottenfeld and Fraumeni cancer epidemiology and prevention. 4th ed. Thun M.J., Linet M.S., Cerhan J.R., Haiman C.A., Schottenfeld D., editors. 2017. Chapter 13: ionizing radiation. [Google Scholar]
- 7.Smith M.T., Guyton K.Z., Gibbons C.F., et al. Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect. 2016;124(6):713–721. doi: 10.1289/ehp.1509912. [DOI] [PMC free article] [PubMed] [Google Scholar]