Mendelian randomization analysis unveiling the genetic connection: How psychiatric disorders heighten cancer risk

The potential links between psychiatric disorders and cancer risk have attracted significant attention in recent years. However, the causal relationships between these conditions remain unclear. To assess causality, a Mendelian randomization analysis was conducted using single nucleotide polymorphisms from large-scale European genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was applied as the primary method for causal estimation, with additional sensitivity analyses performed to evaluate potential pleiotropic effects. IVW estimates revealed that bipolar disorder was associated with an increased risk of prostate cancer (odds ratio (OR) = 1.07; 95% confidence interval (CI): 1.003-1.15; P = .04). Genetically predicted depression was causally linked to a significantly higher risk of breast cancer (OR = 2.49; 95% CI: 1.26-4.9; P = .008), particularly in estrogen receptor-positive (ER+) breast cancer (OR = 2.82; 95% CI: 1.17-6.81; P = .02). Schizophrenia was associated with a significantly higher risk of multiple cancer types, including lung cancer (OR = 1.16; 95% CI: 1.03-1.3; P = .01), breast cancer (OR = 1.05; 95% CI: 1.02-1.09; P = .002), ER+ breast cancer (OR = 1.06; 95% CI: 1.02-1.09; P = .002), endometrial cancer (OR = 1.05; 95% CI: 1.002-1.1; P = .04), and ovarian cancer (OR = 1.08; 95% CI: 1.03-1.13; P = .0007). No significant pleiotropy of the instrumental variables was observed. This psycho-oncology study, characterized by minimal pleiotropic effects, provides genetic evidence supporting an increased incidence of various cancers associated with psychiatric disorders. These findings suggest that underlying psychiatric processes may contribute to cancer development.