Association of systemic inflammation with the obesity paradox in cancer: results from multi-cohort studies

Aims This study aimed to explore whether the obesity paradox exists in overall and specific cancers and to investigate the role of systemic inflammation in the obesity paradox. Methods The Cox proportional hazard model was used to explore the relationship between body mass index (BMI) and all-cause mortality. The mediated effect was used to investigate the proportion of systemic inflammation mediating the relationship between BMI and cancer survival risk. Results The survival probability showed a step-like increase with an increase in BMI regardless of pathological stage. Approximately 10.8%–24.0% of the overall association between BMI and all-cause mortality in cancer was mediated by inflammation. In the internal validation, we found evidence of the obesity paradox in all body composition obtained using BIA, with inflammation remaining an important mediating factor. Furthermore, we also validated the existence of the obesity paradox of cancer in NHANES. Systemic inflammation remains an important factor in mediating the association between BMI and prognosis in cancer patients. Conclusions The obesity paradox is prevalent in most cancers, except for hepatic biliary cancer and breast cancer. Inflammation may be one of the true features of the obesity paradox in cancer.