Association Between Triglyceride-Glucose Index and Risk of Cancer: A Systematic Review and Meta-Analysis

Background/Objectives: The triglyceride-glucose (TyG) index, a reliable marker for insulin resistance, is strongly associated with T2DM, hypertension, and cardiovascular disease. Less well known is its relationship with cancer risk. The aim of this study was to quantify the association between the TyG index and risk of different types of cancer. Methods: Publications were searched in the PubMed, Web of Science, and Scopus databases using appropriate keywords. The PICOS framework was used to select the studies, and their quality was evaluated according to the "Newcastle-Ottawa Scale" (NOS). Meta-analysis was performed through a random-effects model using cancer risk parameters (RR: relative risk, OR: odds ratio and HR: hazard ratio) extracted from 26 selected studies associated with TyG index values. The weighted mean difference (WMD) was used to compare the mean of the TyG index in cancer patients to that of the control group. Heterogeneity was assessed by Cochran's Q and I² statistics, while publication bias was evidenced using the Egger test and the Begg test, and funnel plot asymmetry. Results: A higher TyG index value was observed in cancer subjects (9483) compared to healthy controls (978,675) (WMD: 0.23, 95% CI: 0.16-0.31, p < 0.0001, n = 15). A statistically significant increase in cancer risk was associated with the TyG index level, expressed as both a categorical (OR 1.33, 95% CI 1.22-1.45, p < 0.0001, n = 29) and continuous (OR 1.14, 95% CI 1.10-1.19, p < 0.0001, n = 27) variable. The effect was more evident in case-control/cross-sectional studies compared to cohort studies (OR 1.78, 95% CI 1.51-2.09 vs. OR 1.19, 95% CI 1.10-1.29 TyG categorical; OR 1.46, 95% CI 1.21-1.76 vs. OR 1.09, 95% CI 1.05-1.12 TyG continuous). Stratified analysis showed an increased risk of cancer occurrence for gastrointestinal, gynecological, colorectal, breast, and gastric sites, while no association was observed for endometrial, ovarian, prostate, lung or esophageal cancers. Conclusions: Our results evidence an increase in cancer risk associated with higher TyG index values. However, due to the low number of studies, the effect on specific tumor sites was not statistically significant. Additional epidemiological studies with a cohort design are necessary to confirm these associations.