Two-sample Mendelian Randomization Study for Schizophrenia and Cancers

The causal relationship between cancer and schizophrenia remains controversial. Some published studies describing the role of schizophrenia as a protective factor for cancer by cohort studies or meta-analysis, while others have observed the opposite. Here in this article, we investigated potential genetic relationships between schizophrenia and 13 cancers through two-sample Mendelian randomization (2SMR) on public GWAS summary statistics to fill in this gap. Combining cancer eQTL data, we identified the cancer-related genes according to schizophrenia SNP locus and then performed relative downstream analysis. We discovered that the genetic susceptibility to schizophrenia lead to an increasing risk of breast cancer (odds ratio [OR] per log-odds increase in schizophrenia risk: 1.041, 95% confidence interval [CI]: 1.014-1.067, p=0.0026), ovarian cancer (OR, 1.086; 95%CI, 1.031-1.143; p=0.0018), and thyroid cancer (OR, 1.559; 95% CI, 1.055-2.303; p=0.0256). Furthermore, using the eQTL data, we identified the common genes through mapping to the schizophrenia SNP locus. AS3MT, SFXN2 and PCCB are differentially expressed in cancers and AS3MT, SFXN2 have a significant effect on prognosis. In addition, we noticed that schizophrenia will affect the level of thyroid-stimulating hormone (OR, 1.095; 95% CI, 1.006-1.191; p = 0.0354), which may further affect the level of estrogen and the risk of the above three cancers. In sum, under the 2SMR assumption, our findings offers some important insights into a risk-increasing effect of schizophrenia on three cancers risk. AS3MT, SFXN2 and PCCB may be potential biomarkers for preventing breast cancer and thyroid cancer in patients with schizophrenia.