Background: The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight postmenopausal women who were characterized by either the metabolically healthy phenotype or the metabolically unhealthy phenotype. Methods: A large prospective cohort, the Women's Health Initiative, was used. The analytic sample included 5,068 postmenopausal women with BMI 18.5 to <25 kg/m2. Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference; therefore, women with one or none of the four components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs for the association between metabolic phenotype and risk of colorectal cancer. Results: Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer (HR, 1.49; 95% CI, 1.02-2.18) compared with those who were metabolically healthy. Conclusions: A metabolically unhealthy phenotype was associated with higher risk of colorectal cancer among normal-weight women. Impact: Normal-weight women should still be evaluated for metabolic health and appropriate steps taken to reduce their risk of colorectal cancer.
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