早发性结直肠癌患者根据表型的致病种系变异。

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

European Journal of Human Genetics Pub Date : 2025-03-17 DOI:10.1038/s41431-025-01808-x

Antoine Dardenne, Marion Dhooge, Noémie Basset, Albain Chansavang, Julie Metras, Solenne Farelly, Jeanne Netter, Florence Coulet, Patrick R Benusiglio

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引用次数: 0

摘要

我们回顾性评估了268名41岁前诊断为结直肠癌（CRC）的法国成年患者的致病性种系变异（PGV）的患病率，并按表型分层。分析APC、BMPR1A、CDH1、EPCAM、MLH1、MSH2、MSH3、MSH6、MUTYH、NTHL1、POLE、POLD1、PTEN、PMS2、SMAD4、STK11、TP53。总体而言，21.6%的病例携带PGV。错配修复缺陷（MMRd）型CRC （60.1%， MMR基因）和息肉病相关CRC （48%， APC， MUTYH和msh3双等位基因，POLE）的患病率较高。只有2.3%的MMR熟练且无息肉病的患者携带PGV。第三组涉及的基因是POLE和MSH2, 4例中有3例患有两种同步CRC或有CRC家族史。表型特征应考虑到测试决策。评估所有结直肠癌病例检测的成本效益

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Pathogenic germline variants in patients with early-onset colorectal cancer according to phenotype.

We assessed retrospectively the prevalence of pathogenic germline variants (PGV) in 268 French adult patients diagnosed with colorectal cancer (CRC) before age 41, stratified by phenotype. APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH3, MSH6, MUTYH, NTHL1, POLE, POLD1, PTEN, PMS2, SMAD4, STK11 and TP53 were analyzed. Overall, 21.6% of cases carried a PGV. A high prevalence was observed in Mismatch Repair-deficient (MMRd) CRC (60.1%, MMR genes) and polyposis-associated CRC (48%, APC, MUTYH and MSH3-biallelic, POLE). Only 2.3% of patients with MMR proficient and without polyposis carried a PGV. The genes involved in this third group were POLE and MSH2, and three out of four cases had either two synchronous CRC or a CRC family history. Phenotypic features should be taken into account for testing decision. Evaluating the cost-effectiveness of testing all CRC cases < 41 years, as well as how it aligns with the constraints of various healthcare systems, is warranted.

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来源期刊

European Journal of Human Genetics 生物-生化与分子生物学

CiteScore

9.90

自引率

5.80%

发文量

216

审稿时长

2 months

期刊介绍： The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports and reviews in the rapidly expanding field of human genetics and genomics. It covers molecular, clinical and cytogenetics, interfacing between advanced biomedical research and the clinician, and bridging the great diversity of facilities, resources and viewpoints in the genetics community. Key areas include: -Monogenic and multifactorial disorders -Development and malformation -Hereditary cancer -Medical Genomics -Gene mapping and functional studies -Genotype-phenotype correlations -Genetic variation and genome diversity -Statistical and computational genetics -Bioinformatics -Advances in diagnostics -Therapy and prevention -Animal models -Genetic services -Community genetics