Metabolic health and risk of early-onset cancers in obese young adults: Real-world insights from a large cohort study.

Abstract

e22670 Background: Early-onset cancers, typically defined as malignancies occurring in adults under the age of 50, are an emerging public health concern with rising incidence worldwide. Obesity is a major modifiable risk factor contributing to this trend and is strongly associated with cancers affecting the digestive system and hormone-sensitive organs. Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) represent distinct obesity phenotypes, but their differential association with early-onset obesity-associated cancers remains incompletely understood. Additionally, emerging metabolic therapies, including GLP-1 receptor agonists, may hold potential for cancer risk reduction, highlighting the importance of clarifying metabolic risk profiles in young adults. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative network, including adults aged 18–49 years with a diagnosis of obesity (ICD-10-CM E66.9). MUO was defined as obesity with ≥1 diagnosis of hypertension (I10), type 2 diabetes mellitus (E11), or dyslipidemia (E78). MHO was defined as obesity without any of these conditions. Metabolic comorbidities were assessed up to 5 years prior to the index obesity diagnosis. Propensity score matching (1:1) was performed for age, sex, race/ethnicity, personal history of nicotine dependence, and family history of malignant neoplasm (Z80). The primary outcome was incidence of early-onset obesity-associated cancers, including breast (C50), colon (C18), pancreas (C25), endometrium (C54.1), kidney (C64), liver (C22), esophagus (C15), and gallbladder (C23) cancers, within 5 years following the index date. Results: Before matching, 1,293,901 patients with MUO and 1,500,261 patients with MHO were identified. After matching, each cohort included 966,484 patients. Incidence of early-onset obesity-associated cancers was 0.831% in the MUO group (n = 8,027) compared with 0.727% in the MHO group (n = 7,033), with a risk difference of 0.104% (95% CI: 0.079% to 0.128%; p < 0.0001). The risk ratio was 1.143 (95% CI: 1.107 to 1.181), and the odds ratio was 1.144 (95% CI: 1.108 to 1.182). Conclusions: Among young adults with obesity, those with metabolic dysfunction (MUO) had a modest but statistically significant increased risk of early-onset obesity-associated cancers compared with metabolically healthy obese individuals. These findings emphasize the importance of metabolic health in early cancer prevention strategies and support further investigation into targeted metabolic interventions that may reduce obesity-related cancer risk in younger populations.