Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
Division of Breast Surgery, European Institute of Oncology (IEO), IRCCS, Milan, Italy.
J Med Genet. 2022 Apr;59(4):313-317. doi: 10.1136/jmedgenet-2021-108226. Epub 2021 Dec 24.
The objective of this study was to determining the frequency of different sub-types of pathogenic germline mutations in healthy and asymptomatic individuals from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Relevant literature dating from 1998 to 2019 was systematically searched for data on germline mutations. The collected variants were classified according to their subtype into the following classes: missense, non-sense, splicing, insertions and deletions. The χ test was used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was statistically significant. genetic screening data were retrieved for 224 patients with GC and 289 healthy individuals. Among the subjects that had tested positive, splicing mutations were found in 30.4% of the healthy individuals and in 15.2% of the patients with GC (p=0.0076). Missense mutations were also found to occur in healthy subjects with higher frequency (22.2%) than in GC-affected individuals (18.3%), but the difference was not significant in this case. In families meeting the clinical criteria for the HDGC syndrome, splicing and missense germline mutations have been reported to occur with higher frequency in healthy subjects than in patients with cancer. This preliminary observation suggests that not all pathogenic germline mutations confer the same risk of developing GC.
本研究旨在确定遗传性弥漫性胃癌（HDGC）综合征家族中健康无症状个体中不同种系致病性突变的频率。系统性地检索了 1998 年至 2019 年的相关文献，以获取种系突变的数据。收集到的变体根据其亚型分为以下几类：错义、无义、剪接、插入和缺失。使用 χ 检验来估计胃癌（GC）患者和未受影响个体之间观察到的差异是否具有统计学意义。对 224 名 GC 患者和 289 名健康个体进行了遗传筛查数据检索。在检测为阳性的受试者中，在 30.4%的健康个体和 15.2%的 GC 患者中发现了剪接突变（p=0.0076）。在健康受试者中也发现错义突变的发生率较高（22.2%），高于 GC 患者（18.3%），但在这种情况下差异无统计学意义。在符合 HDGC 综合征临床标准的家族中，已经报道了剪接和错义种系突变在健康受试者中的发生率高于癌症患者。这一初步观察表明，并非所有致病性种系突变都具有相同的发展 GC 的风险。
