Redefining Obesity: Metabolic Health as a Predictor of Cancer Risk in Postmenopausal Women
Recent research highlights a nuanced approach to understanding obesity-related cancer risks in postmenopausal women, focusing beyond body mass index (BMI) to metabolic health markers. The study examined the relationship between metabolic dysfunction and the incidence of obesity-related cancers (ORCs), regardless of BMI. Findings suggest that women classified as metabolically unhealthy—whether overweight or of normal weight—are at a higher risk of developing ORCs compared to their metabolically healthy counterparts.
Metabolic health is determined using markers such as blood pressure, cholesterol levels, fasting glucose, and inflammation indicators like high-sensitive C-reactive protein (hs-CRP). These indicators can provide a more accurate assessment of cancer risk than BMI alone. The research used a comprehensive follow-up of over two decades, reinforcing the significance of metabolic health in cancer prevention strategies.
This shift in focus from BMI to metabolic health underscores the need for healthcare strategies that encompass not just weight management but also metabolic health improvement to mitigate cancer risks. Such approaches could lead to more personalized and effective interventions in cancer prevention for postmenopausal women.
Article Information
Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women's Health Initiative
Published in Cancer Prevention Research. By Prasoona Karra et al.
Abstract
Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk, as metabolic dysfunction can occur across BMI levels. We hypothesized that metabolic dysfunction at any BMI increases ORC risk compared with normal BMI without metabolic dysfunction. Postmenopausal women (n = 20,593) in the Women's Health Initiative with baseline metabolic dysfunction biomarkers [blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), and high-sensitive C-reactive protein (hs-CRP)] were included. Metabolic phenotype (metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese) was classified using four definitions of metabolic dysfunction: (i) Wildman criteria, (ii) National Cholesterol Education Program Adult Treatment Panel III, (iii) HOMA-IR, and (iv) hs-CRP. Multivariable Cox proportional hazards regression, with death as a competing risk, was used to assess the association between metabolic phenotype and ORC risk. After a median (IQR) follow-up duration of 21 (IQR, 15-22) years, 2,367 women developed an ORC. The risk of any ORC was elevated among metabolically unhealthy normal weight (HR = 1.12, 95% CI, 0.90-1.39), metabolically healthy overweight/obese (HR = 1.15, 95% CI, 1.00-1.32), and metabolically unhealthy overweight/obese (HR = 1.35, 95% CI, 1.18-1.54) individuals compared with metabolically healthy normal weight individuals using Wildman criteria. The results were similar using Adult Treatment Panel III criteria, hs-CRP alone, or HOMA-IR alone to define metabolic phenotype. Individuals with overweight or obesity with or without metabolic dysfunction were at higher risk of ORCs compared with metabolically healthy normal weight individuals. The magnitude of risk was greater among those with metabolic dysfunction, although the CIs of each category overlapped. Prevention Relevance: Recognizing metabolic dysfunction as a significant risk factor for ORCs underscores the importance of preventive measures targeting metabolic health improvement across all BMI categories.
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