Prophylactic total gastrectomy in germline CDH1 carriers: results across 25 years from a systematic review and meta-analysis.

IF 3.4 2区医学 Q2 GENETICS & HEREDITY

Journal of Medical Genetics Pub Date : 2026-09-21 DOI:10.1136/jmg-2026-111804

Giovanni Corso, Giovanni Quadrini, Vincenzo Bagnardi, Carlo La Vecchia

{"title":"Prophylactic total gastrectomy in germline CDH1 carriers: results across 25 years from a systematic review and meta-analysis.","authors":"Giovanni Corso, Giovanni Quadrini, Vincenzo Bagnardi, Carlo La Vecchia","doi":"10.1136/jmg-2026-111804","DOIUrl":null,"url":null,"abstract":"Background: Prophylactic total gastrectomy (PTG) is a risk-reducing strategy considered in individuals at high risk for diffuse gastric cancer (DGC) associated with germline CDH1 pathogenic variants.Methods: A systematic literature search (PubMed, Scopus) was conducted to identify studies that performed PTGs in CDH1 carriers. Data were analysed using a random-effects generalised linear mixed model. Cochran's Q test was used to assess the heterogeneity between studies. Forest plots were used to display study-specific estimates, and the pooled estimates were calculated within three subsequent cohort periods (2001-2010; 2011-2020; 2021-2025). Statistical analyses were performed using R software.Results: A total of 21 studies were considered out of 302 originally identified, including a total of 967 CDH1 carriers. PTG was performed in 62.9% of CDH1 pathogenic variant carriers. Advanced DGC (>pT1a) was detected in 1.1% and ≤pT1a in 79% in postoperative PTG specimens. The majority of PTGs were reported from North America (58.9%). The pooled proportion of PTG decreased from 83.2% (95% CI 61.0% to 94.0%) in 2001-2010 to 71.0% (95% CI 59.0% to 80.7%) in 2011-2020 and to 67.5% (95% CI 48.9% to 81.8%) in 2021-2025 (p for trend=0.12).Conclusion: About 60% of PTGs were reported from North America. The majority of the lesions were classified as pT1a. PTG indication has been progressively and constantly decreasing during the last years considered. This can be related to the recent genetic analyses reporting a lower DGC risk in CDH1 carriers and with the improvement in detection of early lesions during endoscopy.Prospero registration number: CRD420261368873.","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jmg-2026-111804","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Prophylactic total gastrectomy (PTG) is a risk-reducing strategy considered in individuals at high risk for diffuse gastric cancer (DGC) associated with germline CDH1 pathogenic variants.

Methods: A systematic literature search (PubMed, Scopus) was conducted to identify studies that performed PTGs in CDH1 carriers. Data were analysed using a random-effects generalised linear mixed model. Cochran's Q test was used to assess the heterogeneity between studies. Forest plots were used to display study-specific estimates, and the pooled estimates were calculated within three subsequent cohort periods (2001-2010; 2011-2020; 2021-2025). Statistical analyses were performed using R software.

Results: A total of 21 studies were considered out of 302 originally identified, including a total of 967 CDH1 carriers. PTG was performed in 62.9% of CDH1 pathogenic variant carriers. Advanced DGC (>pT1a) was detected in 1.1% and ≤pT1a in 79% in postoperative PTG specimens. The majority of PTGs were reported from North America (58.9%). The pooled proportion of PTG decreased from 83.2% (95% CI 61.0% to 94.0%) in 2001-2010 to 71.0% (95% CI 59.0% to 80.7%) in 2011-2020 and to 67.5% (95% CI 48.9% to 81.8%) in 2021-2025 (p for trend=0.12).

Conclusion: About 60% of PTGs were reported from North America. The majority of the lesions were classified as pT1a. PTG indication has been progressively and constantly decreasing during the last years considered. This can be related to the recent genetic analyses reporting a lower DGC risk in CDH1 carriers and with the improvement in detection of early lesions during endoscopy.

Prospero registration number: CRD420261368873.

查看原文本刊更多论文

生殖系CDH1携带者预防性全胃切除术：25年来的系统回顾和荟萃分析结果

背景：在与种系CDH1致病变异相关的弥漫性胃癌（DGC）高危人群中，预防性全胃切除术（PTG）是一种降低风险的策略。方法：系统检索文献（PubMed, Scopus），确定对CDH1携带者进行PTGs的研究。数据分析使用随机效应广义线性混合模型。Cochran’s Q检验用于评估研究之间的异质性。森林样地用于显示特定研究的估计值，并在随后的三个队列期间（2001-2010年、2011-2020年、2021-2025年）计算汇总估计值。采用R软件进行统计分析。结果：在最初确定的302项研究中，共有21项研究被纳入考虑，其中包括967名CDH1携带者。62.9%的CDH1致病变异携带者行PTG检查。术后PTG标本中，晚期DGC （>pT1a）占1.1%，≤pT1a占79%。大多数PTGs报告来自北美（58.9%）。PTG的合并比例从2001-2010年的83.2% （95% CI 61.0% - 94.0%）下降到2011-2020年的71.0% (95% CI 59.0% - 80.7%)， 2021-2025年下降到67.5% (95% CI 48.9% - 81.8%)（趋势p =0.12）。结论：约60%的PTGs报告来自北美。大多数病变被分类为pT1a。在过去的几年中，PTG的适应症逐渐减少。这可能与最近的遗传分析报告CDH1携带者DGC风险较低以及内窥镜检查中早期病变检测的改善有关。普洛斯彼罗注册号：CRD420261368873。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Medical Genetics 医学-遗传学

CiteScore

7.60

自引率

2.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.