PhenoAgeAccel mediates the association between metabolic syndrome and cancer risk in males: a cross-sectional NHANES study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background The relationship between metabolic syndrome (MetS) and cancer risk, and the potential mediating role of biological aging as measured by Phenotypic Age Acceleration (PhenoAgeAccel), remains insufficiently characterized.Methods We conducted a cross-sectional study of 12,664 participants from the National Health and Nutrition Examination Survey (NHANES, 1999–2010, 2015–2020). MetS was defined according to established criteria, cancer status was self-reported, and PhenoAgeAccel was derived from clinical biomarkers. Weighted multivariable logistic regression and formal causal mediation analysis were employed.Results After full adjustment, MetS was significantly associated with increased cancer prevalence (OR = 1.338, 95% CI: 1.074–1.666, p = 0.010). This association was more pronounced in males (OR = 2.383, p < 0.05) and adults aged 20–65 years (OR = 1.573, p < 0.05). Mediation analysis revealed that PhenoAgeAccel significantly accounted for 16.5% of the total effect of MetS on cancer (Average Causal Mediation Effect = 0.00352, p < 0.001). Gender stratification indicated a statistically significant mediating effect in males (proportion mediated = 10.9%, p = 0.002) but not in females (proportion mediated = 10.9%, p = 0.086). The direct effect of MetS remained significant (OR = 1.265, p = 0.050).Conclusion MetS is associated with elevated cancer risk, with PhenoAgeAccel serving as a significant mediating pathway, particularly among males. These findings identify younger males as a high-risk subgroup for targeted preventive strategies.
Source: The Aging Male
Language: English
Topic: Cancer Risks and Factors
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,557
Award: G4218789487
OpenAlex ID: W7118986287