Triglyceride-Glucose Index, Modifiable Lifestyle, and Risk of Colorectal Cancer: A Prospective Analysis of the Korean Genome and Epidemiology Study.

Background: Insulin-mediated pathways plausibly explain the pathogenesis of colorectal cancer (CRC). The triglyceride-glucose index (TyG) is a surrogate of insulin resistance (IR), but its association with CRC in the Korean population has not been evaluated.

Methods: From the 2004-2013 Korean Genome and Epidemiology Study, 98,800 participants aged 40-69 years were followed through 2020. Data on CRC incidence were obtained from the Korean National Cancer Center registry. Cox regression models and restricted cubic splines were fitted to examine the association between the TyG; In [(triglycerides) × (fasting glucose)/2] and CRC incidence. Joint effects of modifiable lifestyle factors and TyG on CRC risk were also investigated.

Results: Median follow-up time was 10.6 years, and 699 CRC cases were observed. A unit-increment in TyG was associated with increased risk of CRC combined (hazard ratio, HR: 1.28, and 95% confidence interval, CI: 1.12-1.46), colon (1.29, 1.10-1.54), and rectal cancer (1.24, 1.01-1.52). Associations were dose-dependent, with linear associations observed for CRC and colon, but non-linear associations were observed for rectal cancer. A high TyG index (above 8.4) combined with overweight/obesity was linked to an increased risk of CRC (1.31, 1.07-1.61) and colon cancer (1.33, 1.03-1.72). When combined with low fruit and vegetable intake, the risks were higher for CRC (1.40, 1.12-1.74) and colon cancer (1.57, 1.18-2.09). Combined with high red meat consumption, the risks were elevated for CRC (1.32, 1.05-1.65) and colon cancer (1.52, 1.15-2.02).

Conclusions: A high TyG index was associated with a higher risk of colorectal cancer, and the risk was highest among participants with a high BMI, low fruit and vegetable intake, and high intake of red meat, suggesting a role of both insulin resistance and modifiable lifestyle in colorectal cancer development.