Little is known about obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk. We investigated body mass index jointly and in interaction with metabolic health status in relation to obesity-related cancer risk among 797,193 European individuals in Me-Can 2.0. Metabolic aberrations were proxied by a metabolic score of mid-blood pressure, plasma glucose and triglycerides. After up to 40 years of follow-up, we recorded 23,630 obesity-related cancers.
We found that metabolic aberrations further increased the obesity-induced cancer risk. Metabolically unhealthy obesity was associated with an increased risk of colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer, with the highest risk estimates for endometrial, liver, and renal cell cancer. Metabolically healthy obesity showed a higher relative risk for colon (in men), endometrial, renal cell, liver, and gallbladder cancer, though the risk relationships were weaker. There were no multiplicative interactions. However, we found additive, positive interactions between BMI and metabolic health status on obesity-related and rectal cancer among men, and on endometrial cancer, suggesting that obesity jointly with metabolic aberrations increase the risk of these cancers more than expected from the sum of their individual parts. This study illustrates that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk. Overall, both obesity and metabolic aberrations are useful targets for the prevention of obesity-related cancers. The study has been published in the Journal of the National Cancer Institute.