Abstract
BACKGROUND: Obesity and metabolic syndrome (MetS) appear in clusters and are both associated with an increased risk of cancer. However, it remains unknown whether obesity status with or without MetS increases the risk of site-specific cancers. METHODS: We used data derived from 390,575 individuals (37-73 years old) from the UK Biobank who were enrolled from 2006-2016 with a median of 7.8 years of follow-up. Obesity was defined by BMI ≥ 30 kg/m(2) and MetS was defined by the criteria of the Adult Treatment Panel-III (ATP-III). Cox proportional hazards models were used to investigate the associations of BMI and MetS with 22 cancers. RESULTS: Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) phenotypes represented 6.7% and 17.9% of the total analytic samples and 27.1% and 72.9% of the included subpopulation with obesity, respectively. Obesity was independently associated with higher risks of 10 of 22 cancers. Stratified by metabolic status, the MUO phenotype was consistently associated with 10 obesity-related cancers. In contrast, the MHO phenotype was only associated with increased risks of five cancers: endometrium, oesophagus, kidney, pancreas and postmenopausal breast cancers. CONCLUSION: Even in metabolically healthy individuals, obesity was associated with increased risks of five cancers, whereas we did not find that these individuals were associated with increased risks of several other obesity-related cancers.