Prospective analysis of the relationship between four insulin resistance indicators and esophageal cancer risk using UK biobank data

Introduction: This study aimed to examine the relationship between four insulin resistance (IR) markers—triglyceride-glucose (TyG) index, TyG combined with body mass index (TyG-BMI), the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and the metabolic score for insulin resistance (METS-IR)—and the risk of developing esophageal cancer.

Methods: Data were analyzed from 388,900 participants enrolled in the UK Biobank between 2006 and 2010. The associations between the IR surrogates and the incidence of esophageal cancer, specifically esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), were evaluated using Fine-Gray competing risk models, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) curves.

Results: Over a median follow-up of ten years, esophageal cancer was diagnosed in 0.16% (95% CI: 0.11–0.26%) of participants, and the mortality rate reached 4.17% (95% CI: 3.86–4.46%). Each standard deviation increase in TyG, TyG-BMI, TG/HDL-C, and METS-IR was associated with elevated EAC risk, with hazard ratios (HRs) of 1.16, 1.37, 1.08, and 1.36, respectively (all P<0.05). Conversely, the same increases were linked to reduced ESCC risk, with HRs of 0.80, 0.67, 0.77, and 0.65, respectively. The RCS analysis suggested that most of these associations were nonlinear (P<0.05). Among the four markers, METS-IR demonstrated the strongest predictive capability based on ROC curve analysis.

Conclusion: The study found significant associations between TyG, TyG-BMI, TG/HDL-C, and METS-IR with the risks of both EAC and ESCC. METS-IR emerged as the most effective predictor among the four, indicating its potential as a useful tool for early detection and risk stratification of esophageal cancer.

Publication History

Article published online:
04 September 2025