Metabolic Phenotypes and the Risk of Cancer Occurrence: A Prospective Cohort Study with 18-Year Follow-up

Background: Current evidence concerning a link between metabolic phenotypes and their dynamic changes over time and the risk of cancer is limited. The present study aimed to assess the association between different metabolic health statuses and the risk of cancer occurrence among adult individuals. Methods: This prospective cohort study enrolled 11,445 adults aged ≥18 years from the Tehran Lipid and Glucose Study and followed them for 18 years. We identified metabolic phenotypes based on the Joint Interim Statement. Accordingly, participants were divided into four groups: metabolically healthy normal weight/overweight (MHNW/OW), metabolically unhealthy normal weight/overweight (MUNW)/OW, metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). Cox proportional hazards modeling was performed to assess the association between metabolic phenotype and the risk of cancer occurrence. Results: The multivariable adjusted hazard ratio (HR) (95% confidence interval [CI]) for cancer risk in participants with the MUNW/OW phenotype was 1.37 (95% CI, 1.04 to 1.82) and that in those with the MUO phenotype was 1.84 (95% CI, 1.21 to 2.79) when compared to those with the MHNW/OW phenotype, respectively. More particularly, the risk of breast cancer was higher in women with the MHO phenotype (HR, 3.60; 95% CI, 1.34 to 9.60) as well as those with the MUO phenotype (HR, 4.69; 95% CI, 1.96 to 11.20) relative to those with the MHNW/OW phenotype. Ultimately, however, we found no relationship between phenotype transition and the risk of cancer occurrence. Conclusion: Based on our findings, metabolically unhealthy phenotypes may be associated with a higher overall incidence of cancer. In addition, obesity, independent of metabolic status, was linked to an increased risk of breast cancer incidence. No association between the transition from a metabolically healthy to unhealthy phenotype and cancer risk was established.