Hillside Hospital, North Shore-Long Island Jewish Health System, Department of Psychiatry Research, Glen Oaks, NY 11004, USA.
Am J Psychiatry. 2010 Apr;167(4):436-43. doi: 10.1176/appi.ajp.2009.09050615. Epub 2010 Jan 15.
Despite increased exposure to cancer risk factors, several studies have demonstrated a lower incidence of cancer in schizophrenia patients than in the general population. Lower cancer rates in first-degree relatives of schizophrenia patients suggest that the inverse relationship between cancer and schizophrenia may be related to genetic factors. Few studies of schizophrenia have focused on cancer-related genes. The MET proto-oncogene is primarily linked to tumor metastasis, but MET is also involved in neurodevelopment and influences risk for autism. Thus, MET may be of particular interest as a candidate gene for neuropsychiatric diseases with a developmental etiology, including schizophrenia.
The authors examined the relationship between 21 single-nucleotide polymorphisms in MET and schizophrenia in 173 Caucasian patients and 137 comparison subjects. They then genotyped a second independent sample (107 patients and 112 comparison subjects) for replication. Finally, they tested for MET's effects on general cognitive ability (g).
In the initial cohort, the authors identified four haplotype blocks and found one block to be globally associated with schizophrenia. In block 3, the most common haplotype was overrepresented in comparison subjects (frequency, 47%) relative to schizophrenia patients (frequency, 33%) (p=4.0 x 10(-4); odds ratio=0.56). The authors replicated the block 3 finding in the second sample with similar frequencies: 46% in comparison subjects and 36% in schizophrenia patients (p=0.03; odds ratio=0.66). Moreover, the protective haplotype was associated with a higher g in the combined comparison sample.
These data suggest that MET variation influences schizophrenia risk and neurocognition, supporting a neurodevelopmental role across CNS-relevant phenotypes. These results add to the growing evidence suggesting an intriguing relationship between cancer-related genes and schizophrenia susceptibility.
尽管接触到更多的癌症风险因素，一些研究表明精神分裂症患者的癌症发病率低于普通人群。精神分裂症患者一级亲属的癌症发病率较低，这表明癌症与精神分裂症之间的反比关系可能与遗传因素有关。很少有研究关注与癌症相关的精神分裂症基因。MET 原癌基因主要与肿瘤转移有关，但 MET 也参与神经发育，并影响自闭症的风险。因此，MET 可能是一个特别有趣的候选基因，因为它与具有发育病因的神经精神疾病有关，包括精神分裂症。
作者研究了 173 名白种人患者和 137 名对照受试者中 MET 的 21 个单核苷酸多态性与精神分裂症之间的关系。然后，他们对第二个独立样本（107 名患者和 112 名对照）进行基因分型以进行复制。最后，他们测试了 MET 对一般认知能力（g）的影响。
在最初的队列中，作者确定了四个单倍型块，发现一个块与精神分裂症总体相关。在第 3 块中，与精神分裂症患者（频率为 33%）相比，常见的单倍型在对照受试者中更为常见（频率为 47%）（p=4.0×10(-4)；优势比=0.56）。作者在第二个样本中复制了第 3 块的发现，其频率相似：对照受试者中为 46%，精神分裂症患者中为 36%（p=0.03；优势比=0.66）。此外，保护性单倍型与合并对照样本中的 g 较高相关。
这些数据表明，MET 变异影响精神分裂症风险和神经认知，支持 CNS 相关表型的神经发育作用。这些结果增加了越来越多的证据，表明癌症相关基因与精神分裂症易感性之间存在有趣的关系。
