TY - JOUR
T1 - Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women’s Health Initiative
AU - Karra, Prasoona
AU - Hardikar, Sheetal
AU - Winn, Maci
AU - Anderson, Garnet L.
AU - Haaland, Benjamin
AU - Shadyab, Aladdin H.
AU - Neuhouser, Marian L.
AU - Seguin-Fowler, Rebecca A.
AU - Thomson, Cynthia A.
AU - Coday, Mace
AU - Wactawski-Wende, Jean
AU - Stefanick, Marcia L.
AU - Zhang, Xiaochen
AU - Cheng, Ting Yuan David
AU - Karanth, Shama
AU - Sun, Yangbo
AU - Saquib, Nazmus
AU - Pichardo, Margaret S.
AU - Jung, Su Yon
AU - Tabung, Fred K.
AU - Summers, Scott A.
AU - Holland, William L.
AU - Jalili, Thunder
AU - Gunter, Marc J.
AU - Playdon, Mary C.
N1 - Publisher Copyright:
©2024 American Association for Cancer Research.
PY - 2025/2/1
Y1 - 2025/2/1
N2 - 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 ¼ 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 ¼ 1.12, 95% CI, 0.90–1.39), metabolically healthy overweight/obese (HR ¼ 1.15, 95% CI, 1.00–1.32), and metabolically unhealthy overweight/obese (HR ¼ 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.
AB - 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 ¼ 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 ¼ 1.12, 95% CI, 0.90–1.39), metabolically healthy overweight/obese (HR ¼ 1.15, 95% CI, 1.00–1.32), and metabolically unhealthy overweight/obese (HR ¼ 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.
UR - https://www.scopus.com/pages/publications/85218222843
U2 - 10.1158/1940-6207.CAPR-24-0082
DO - 10.1158/1940-6207.CAPR-24-0082
M3 - Article
C2 - 39540294
AN - SCOPUS:85218222843
SN - 1940-6207
VL - 18
SP - 63
EP - 72
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 2
ER -