Mental health and malignancy: Real-world associations between early-onset gastrointestinal cancers and mental illness.

11174 Background: Although progress has been made in reducing overall cancer incidence, early-onset cancers have continued their troublesome rise. Similarly, the incidence and/or prevalence of psychiatric disorders has increased, particularly among young adults. Mental illness may influence cancer development, however, real-world evidence linking mental illness to early-onset gastrointestinal cancers is limited. Methods: We sought to conduct a real-world, retrospective cohort study using the TriNetX United States Research Database, a federated network of de-identified electronic health records from over 70 healthcare organizations, to examine this association. Adults aged 18–50 years with at least one of five pre-determined core mental illnesses, including generalized anxiety disorder (GAD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bipolar disorder, and/or schizophrenia, were compared with same-aged individuals without any of the core mental illnesses. A five-year lookback period was used from January 25th, 2021 to January 25th 2026. Propensity score matching adjusted for demographic and clinical confounders. Incidence of early-onset cancers diagnosed were then assessed during five-year follow-up. Sensitivity analyses required a ≥ 1-year lag between mental illness diagnosis and cancer onset. Results: 2,911,432 patients ages 18-50 were identified as having a core mental illness, whereas 21,439,614 patients ages 18-50 were identified as not having any core mental illness. All-cause mental illness was associated with an increased risk of developing early-onset gastric cancer (RR 1.451, CI 1.189-1.771, p < 0001), pancreatic cancer (RR 1.566, CI 1.328-1.822, p < 0.0001) and colorectal cancer (RR 1.407, CI 1.313-1.506, p < 0.0001). Associations with early-onset esophageal cancer, biliary tract cancer, and small intestine cancer did not meet thresholds for statistical significance. In addition, subgroup analysis was completed for each core mental illness. GAD was associated with an increased risk of developing early-onset pancreatic cancer (RR 1.627, CI 1.220-2.169, p < 0.0001), small intestine cancer (RR 2.435, CI 1.498-3.956, p < 0.0001), and colorectal cancer (RR 1.625, CI 1.441-1.833, p < 0.0001). MDD was only associated with an increased risk of developing early-onset colorectal cancer (RR 1.425, CI 1.213-1.674, p < 0.0001). OCD, bipolar disorder, and schizophrenia had no statistically significant association with the development of the early-onset cancers noted above. Conclusions: In this large, real-world cohort study, all-cause mental illness, GAD, and MDD were associated with an increased risk of several early-onset gastrointestinal cancers. These findings suggest that one’s mental health represents a potentially modifiable risk factor in early-onset gastrointestinal cancers and warrants further investigation.