dbMMR-Chinese database: the first public database of DNA mismatch repair gene variation in Chinese population

Mutation in DNA mismatch repair genes (MMR) is the genetic predisposition for multiple types of cancer as represented by the Lynch syndrome. Identification of MMR mutation carrier without cancer is critical for their cancer prevention and these with cancer for effective treatment. China has the largest population size and the largest cancer cases in the world. However, comprehensive MMR mutation knowledge in this population remains elusive. We performed an extensive data mining, standardization, and annotation for MMR variation data derived from 53,917 Chinese individuals, including 25,013 cancer cases and 28,904 non-cancer cases. We identified 21,376 distinct MMR variants including 1,894 in coding regions and19,482 in non-coding regions in four MMR genes of MLH1, MSH2, MSH6 and PMS2. Using the data, we developed an open-access public database dbMMR-Chinese (https://dbMMR-chinese.fhs.um.edu.mo), which is the largest one from a single non-Caucasian ethnic population.

DNA错配修复基因（DNA mismatch repair, MMR）的突变是多种癌症的遗传易感因素，以林奇综合征（Lynch syndrome）为典型代表。对未罹患癌症的MMR突变携带者进行识别，对其癌症预防工作至关重要；而对已罹患癌症的MMR突变携带者进行识别，则可为其开展有效治疗提供关键支持。中国是全球人口规模最大、癌症病例数最多的国家，但针对该人群的全面MMR突变相关认知仍较为匮乏。本研究针对来自53917名中国个体的MMR变异数据开展了大规模数据挖掘、标准化处理与注释工作，研究对象涵盖25013例癌症患者与28904名非癌症个体。我们在MLH1、MSH2、MSH6及PMS2这4个MMR基因中，共鉴定出21376种不同的MMR变异，其中包括1894种编码区变异与19482种非编码区变异。基于上述数据，我们开发了开放获取的公共数据库dbMMR-Chinese（https://dbMMR-chinese.fhs.um.edu.mo），该数据库是目前全球规模最大的单非高加索族裔人群MMR突变数据库。