Background Studies of obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk are scarce. Methods We investigated body mass index (BMI, normal weight/overweight/obesity) jointly and in interaction with metabolic health status in relation to obesity-related cancer risk (n = 23,630) among 797,193 European individuals. A metabolic score comprising mid-blood pressure, plasma glucose and triglycerides was used to define metabolically healthy and unhealthy status. Hazard ratios (HRs) and multiplicative interactions were assessed using Cox regression, and additive interactions were assessed using the relative excess risk for interaction. All statistical tests were two-sided. Results Metabolically unhealthy obesity, with a baseline prevalence of 7%, was, compared to metabolically healthy normal weight, associated with an increased relative risk of any obesity-related cancer and of colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer (p < 0.05), with the highest risk estimates for endometrial, liver, and renal cell cancer (HRs, 2.55 to 3.00). Metabolically healthy obesity showed a higher relative risk for any obesity-related cancer and colon (in men), endometrial, renal cell, liver, and gallbladder cancer, though the risk relationships were weaker. There were no multiplicative interactions, but there were additive, positive interactions between BMI and metabolic health status on obesity-related and rectal cancer among men, and on endometrial cancer (p < 0.05). Conclusions This study highlights that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk. In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that both obesity and metabolic aberrations are useful targets for prevention.
Physical activity (PA) has been associated with a lower risk of some obesity‐related cancers, but the combined association and interaction of PA and body weight on obesity‐related cancer risk is less clear. We examined the association of leisure‐time PA (high/low) and its combination with body mass index (BMI, <25 [low]/≥25 [high] kg/m2) on obesity‐related cancer risk in 570 021 individuals, aged 43 years on average at baseline, in five Scandinavian cohorts. We used Cox regression to calculate hazard ratios of obesity‐related cancers (n = 19 074) and assessed multiplicative and additive interactions between PA and BMI on risk. High leisure‐time PA, recorded in 19% of the individuals, was associated with a 7% (95% confidence interval [CI] 4%‐10%) lower risk of any obesity‐related cancer compared to low PA, with similar associations amongst individuals with a low and a high BMI (6% [1%‐11%] and 7% [2%‐11%]). High PA was also associated with decreased risks of renal cell (11% [9%‐31%]) and colon cancer (9% [2%‐16%]). When high PA and low BMI were combined, the relative risk reduction for all obesity‐related cancers was 24% (95% CI 20%‐28%); endometrial cancer, 47% (35%‐57%); renal cell cancer, 39% (27%‐51%); colon cancer, 27% (19%‐35%); multiple myeloma, 23% (2%‐40%) and pancreatic cancer, 21% (4%‐35%), compared to low PA‐high BMI. There were no additive or multiplicative interactions between PA and BMI on risk. The result of our study suggests a reduced risk of obesity‐related cancer by leisure‐time PA in both normal weight and overweight individuals, which further decreased for PA and normal weight combined.
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