Corso Giovanni, Corso Federica, Bellerba Federica, Carneiro Patrícia, Seixas Susana, Cioffi Antonio, La Vecchia Carlo, Magnoni Francesca, Bonanni Bernardo, Veronesi Paolo, Gandini Sara, Figueiredo Joana
Division of Breast Surgery, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy.
Cancers (Basel). 2021 Mar 12;13(6):1269. doi: 10.3390/cancers13061269.
Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by germline mutations. Nevertheless, current genetic screening recommendations disregard an unbalanced worldwide distribution of variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing variants in gastric cancer patients originating from both high- and low-prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that mutations are more frequently identified in gastric cancer low-incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high-incidence areas of gastric cancer, when compared with non-missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease.
遗传性弥漫性胃癌（HDGC）是一种由种系突变引起的复杂的多因素遗传性癌症易感性综合征。然而，目前的基因筛查建议忽视了变异在全球分布的不均衡性，这影响了检测效果和患者管理。在这项系统评价中，我们收集并分析了所有描述来自高患病率和低患病率国家的胃癌患者变异情况的研究。根据HDGC基因检测临床标准的实施情况，将所选研究分为家族研究、系列研究和未知研究。我们的结果表明，在胃癌低发病率国家以及包括符合标准病例的家族研究组中，更常发现突变。考虑到变异的类型，我们证实突变类型的相对频率在研究组和地理区域内有所不同。在系列研究中，与非错义突变相比，胃癌高发病率地区的错义变异频率更高。然而，应用假定相关性的变异评分导致赋予胃癌风险增加的变异大幅减少。在此，我们证明基因筛查标准对于识别携带具有临床意义突变的个体至关重要。此外，我们建议未来的检测指南应考虑不同地理区域的胃癌发病率，以改进监测计划和疾病的早期诊断。
