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

11173 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 hormone-related cancers is limited. Methods: We conducted 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 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 and propensity score matching was used to adjust for 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 were identified as having a core mental illness, whereas 21,439,614 patients were identified as not having any core mental illness. All-cause mental illness was associated with an increased risk of developing early-onset breast cancer (RR 2.253, CI 2.149-2.362, p < 0.0001), uterine cancer (RR 1.711, CI 1.515-1.934, p < 0.0001), and ovarian cancer (RR 1.984, CI 1.790-2.198, p < 0.0001). Associations with early-onset prostate cancer and testicular cancer did not meet thresholds for statistical significance. Within the subgroup analysis, GAD was associated with an increased risk of developing early-onset breast cancer (RR 2.565, CI 2.398-2.742, p < 0.0001), uterine cancer (RR 1.534, CI 1.278-1.841, p < 0.0001) and ovarian cancer (RR 1.736, CI 1.492-2.019, p < 0.0001). MDD was associated with early-onset breast cancer (RR 2.380, CI 2.161-2.622, p < 0.0001), uterine cancer (RR 2.089, CI 1.625-2.685, p < 0.0001), and ovarian cancer (RR 1.983, CI 1.591-2.472, p < 0.0001). Bipolar disorder was associated only with early-onset breast cancer (RR 1.415, CI 1.244-1.610, p < 0.0001). OCD and schizophrenia had no statistically significant associations. Conclusions: In this large, real-world cohort study, all-cause mental illness, GAD, and MDD were associated with an increased risk of early-onset hormonal cancers more commonly affecting female patients. These findings suggest that mental health represents a potential modifiable risk factor in early-onset, hormone-related cancers and warrants further investigation.