Association between proxy markers of insulin resistance and colorectal cancer risk: results from a large scale prospective cohort of Korean adults

Background : Colorectal cancer (CRC) remains one of the most common cancers in Korea, underscoring the importance of identifying modifiable risk factors. Although insulin resistance has been implicated in CRC development, existing evidence remains inconsistent, and direct measures of insulin resistance are not routinely collected in clinical practice. This limitation highlights the potential utility of simple proxy markers of insulin resistance in epidemiologic and clinical settings. In this study, we investigated the associations between several proxy insulin resistance markers and CRC risk among Korean adults. Methods: Using data from the Korean Genome and Epidemiology Study Health Examinee cohort, we evaluated the associations between several proxy markers of insulin resistance, including the TG/HDL ratio, triglyceride-glucose index (TyG), TyG-BMI index, TyG-waist circumference index (TyG-WC), TyG-waist-to-height ratio index (TyG-WHTR), and the metabolic score for insulin resistance (METS-IR), and CRC risk using Cox regression models. Subgroup analyses were stratified by sex, age, diabetes status, and prior screening experience, and sensitivity analyses were conducted based on varying follow-up durations. Results: During a median follow-up period of 9.3 years, 795 new CRC cases were observed among 106,965 Koreans aged 40-69 years (36,899 men and 70,066 women). For the TG/HDL ratio, individuals in the highest quartile had a significantly elevated CRC risk compared with the lowest quartile (HR: 1.23, 95% CI: 1.00-1.53). A similar pattern was observed for the TyG and TyG-WC indices, where quartile 4 was associated with increased CRC incidence (TyG Q4 HR: 1.30, 95% CI: 1.04-1.63; TyG-WC Q4 HR: 1.36, 95% CI: 1.01-1.83). Finally, the METS-IR index showed a graded association, and the highest quartile was significantly associated with CRC incidence (Q4 HR: 1.26, 95% CI: 1.02-1.57). Conclusions: In this large population-based cohort, multiple surrogate markers of insulin resistance were independently associated with an increased risk of colorectal cancer, with the strongest effects observed in the highest quartiles. These findings indicate that metabolic dysregulation related to insulin resistance contributes to colorectal carcinogenesis and that simple lipid-glucose-anthropometric markers may help identify individuals at elevated risk.