Cancer Risk in Normal Weight Individuals with Metabolic Obesity: A Narrative Review

Abstract

Obesity represents one of the most significant public health challenges worldwide. Current clinical practice relies on body mass index (BMI) to define the obesity status of an individual, even though the index has long been recognized for its limitations as a measure of body fat. In normal BMI individuals, increased central adiposity has been associated with worse health outcomes, including increased risks of cardiovascular disease and metabolic disorders. The condition leading to these outcomes has been described as metabolic obesity in the normal weight (MONW). More recent evidence suggests that MONW is associated with increased risk of several obesity-related malignancies, including postmenopausal breast, endometrial, colorectal, and liver cancers. In MONW patients, the false reassurance of a normal range BMI can lead to lost opportunities for implementing preventive interventions that may benefit a substantial number of people. A growing body of literature has documented the increased risk profile of MONW individuals and demonstrated practical uses for body composition and biochemical analyses to identify this at-risk population. In this review, we survey the current literature on MONW and cancer, summarize pathophysiology and oncogenic mechanisms, highlight potential strategies for diagnosis and treatment, and suggest directions for future research.

Figure 1.

Metabolic obesity in the normal weight and its clinical significance. Abbreviations: BMI, body mass index; MHNW, metabolically healthy normal weight; MONW, metabolically obese normal weight; OW/OB, overweight/obese; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; CRP, C-reactive protein; SHBG, sex hormone binding globulin; DXA, dual-energy X-ray absorptiometry; BIA, bioelectrical impedance analysis.

Figure 2.

Local and systemic effects of metabolic obesity and mechanisms for cancer promotion. Abbreviations: CLS, crown-like structures; IL-6, interleukin-6; IL-10, interleukin-10; IL-18, interleukin-18; MCP-1, monocyte chemoattractant protein-1; TGF-β1, transforming growth factor-β1; SHBG, sex hormone binding globulin; CRP, C-reactive protein; IGF-1, insulin-like growth factor-1; IGFBP, insulin-like growth factor binding protein; FA, fatty acids; PI3K, phosphoinositide 3-kinase; VEGF, vascular endothelial growth factor.

Figure 3.

Methods of body composition measurement and their diagnostic outputs. A: BIA with mock report of body composition data. B: DXA machine and a whole-body DXA scan. C: MRI machine and an axial abdominal MRI scan. D: CT Imager with axial abdominal CT scan. Abbreviations: BIA, bioelectrical impedance analysis; DXA, dual-energy X-ray absorptiometry; MRI, magnetic resonance imaging; CT, computed tomography.