Most women with epithelial ovarian cancer (EOC) present with late-stage disease. As a result, globally, EOC is responsible for >150,000 deaths a year. Thus, a better understanding of risk factors for developing EOC is crucial for earlier screening and detection to improve survival. To that effort, there have been suggestions that there is an association of schizophrenia and cancer, possibly because metabolic changes are a hallmark of both cancer and schizophrenia (SZ). Perturbed choline metabolism has been documented in both diseases. Our objective was to use Mendelian randomization to evaluate whether SZ increased risk for developing EOC or the converse, and, whether SZ impacted 1- or 2-glycerophosphocholine (1- or 2-GPC) metabolites. We found that SZ conferred a weak but increased risk for EOC, but not the reverse (no evidence that EOC caused SZ). SZ was also causally associated with lower levels of two 1- or 2-GPC species and with suggestively lower levels in an additional three 1- or 2-GPCs. We postulate that perturbed choline metabolism in SZ may mimic or contribute to a “cholinic” phenotype, as observed in EOC cells.

大多数患有上皮性卵巢癌（EOC）的妇女都患有晚期疾病。结果，在全球范围内，EOC每年导致超过15万人死亡。因此，更好地了解发展EOC的危险因素对于早期筛查和发现以提高生存率至关重要。为此，有人建议精神分裂症与癌症有关，可能是因为代谢变化是癌症和精神分裂症（SZ）的标志。在这两种疾病中都有胆碱代谢紊乱的记录。我们的目标是使用孟德尔随机法评估SZ是否增加发生EOC的风险或发生EOC的风险，以及SZ是否影响1-或2-甘油磷酸胆碱（1-或2-GPC）的代谢产物。我们发现SZ赋予EOC的风险微弱但增加了，但并非相反（没有证据表明EOC造成了SZ）。SZ还与两个1或2-GPC物种的较低水平以及其他三个1或2-GPC的暗示水平较低有因果关系。我们推测，如在EOC细胞中观察到的那样，SZ中胆碱代谢紊乱可能会模仿或促成“胆碱”表型。