The aims of the Prospective Lynch Syndrome Database (PLSD) are to provide empirical prospectively observed data on the incidences of cancer in different organs, survival following cancer and the effects of interventions in carriers of pathogenic variants of the mismatch repair genes ( path_MMR ) categorized by age, gene and gender. Although PLSD is assumption-free, as with any study the ascertainment procedures used to identify the study cohort will introduce selection biases which have to be declared and considered in detail in order to provide robust and valid results. This paper provides a commentary on the methods used and considers how results from the PLSD reports should be interpreted. A number of the results from PLSD were novel and some in conflict with previous assumptions. Notably, colonoscopic surveillance did not prevent colo-rectal cancer, survival after colo-rectal, endometrial and ovarian cancer was good, no survival gain was observed with more frequent colonoscopy, new causes of cancer-related death were observed in survivors of first cancers due to later cancers in other organs, variants in the different MMR genes caused distinct multi-cancer syndromes characterized by different penetrance and phenotypes. The www.PLSD.eu website together with the InSiGHT database website ( https://www.insight-group.org/variants/databases/ ) now facilitate evidence-based personalized precision health care for individual carriers at increased risk of cancer. The arguments are summarized in a final discussion on how to conceptualize current knowledge for the different practical purposes of treating cancers, genetic counselling and prevention, and for understanding /research on carcinogenetic mechanisms.

中文翻译：

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前瞻性林奇综合征数据库报告支持基于证据的个人精准医疗保健

前瞻性林奇综合征数据库 (PLSD) 的目的是提供关于不同器官癌症发病率、癌症后存活率以及干预措施对错配修复基因 (path_MMR) 致病变异携带者的影响的实证前瞻性观察数据年龄、基因和性别。尽管 PLSD 是无假设的，但与任何研究一样，用于识别研究队列的确定程序将引入选择偏倚，必须详细声明和考虑这些偏倚，以提供可靠和有效的结果。本文对所使用的方法进行了评论，并考虑了应如何解释 PLSD 报告的结果。PLSD 的许多结果是新颖的，有些与之前的假设相冲突。尤其，结肠镜监测并不能预防结肠直肠癌，结肠直肠癌、子宫内膜癌和卵巢癌术后生存率良好，更频繁的结肠镜检查没有观察到生存率增加，在第一次癌症的幸存者中观察到新的癌症相关死亡原因与其他器官的癌症不同，不同 MMR 基因的变异导致不同的多癌综合征，其特征是不同的外显率和表型。www.PLSD.eu 网站与 InSiGHT 数据库网站 (https://www.insight-group.org/variants/databases/) 现在为癌症风险增加的个体携带者提供基于证据的个性化精准医疗保健。在最后的讨论中总结了这些论点，即如何将当前知识概念化以用于治疗癌症的不同实际目的，