Dardenne Antoine, Dhooge Marion, Basset Noémie, Chansavang Albain, Metras Julie, Farelly Solenne, Netter Jeanne, Coulet Florence, Benusiglio Patrick R
Sorbonne Université, Service de Chirurgie digestive, Hôpital Saint-Antoine, APHP, Paris, France.
Paris Cité Université, Service de Gastroentérologie et Oncologie digestive, UF d'Oncogénétique digestive, Hôpital Cochin, APHP, Paris, France.
Eur J Hum Genet. 2025 Mar 17. doi: 10.1038/s41431-025-01808-x.
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.
我们对268例41岁之前被诊断为结直肠癌（CRC）的法国成年患者进行了回顾性评估，根据表型进行分层，分析了APC、BMPR1A、CDH1、EPCAM、MLH1、MSH2、MSH3、MSH6、MUTYH、NTHL1、POLE、POLD1、PTEN、PMS2、SMAD4、STK11和TP53等基因的致病种系变异（PGV）发生率。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）中观察到高发生率。错配修复功能正常且无息肉病的患者中只有2.3%携带PGV。第三组涉及的基因是POLE和MSH2，四分之三的病例有两个同步发生的CRC或CRC家族史。检测决策应考虑表型特征。评估对所有41岁以下CRC病例进行检测的成本效益，以及其如何符合各种医疗保健系统的限制是有必要的。
