Second malignancies in patients with deficient mismatch repair system/microsatellite instability-high colorectal cancer.

IF 3.4 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Therapeutic Advances in Gastroenterology Pub Date : 2025-06-21 eCollection Date: 2025-01-01 DOI:10.1177/17562848251347375

Paul Franques, Pierre Moreau, Camille Evrard, Arnaud Chong-Si-Tsaon, Éric Frouin, Marie-Luce Auriault, Valérie Moulin, Audelaure Junca, Julie Godet, Lucie Lebeau, Roxane Aguillon, Gaëlle Tachon, Lucie Karayan-Tapon, David Tougeron

{"title":"Second malignancies in patients with deficient mismatch repair system/microsatellite instability-high colorectal cancer.","authors":"Paul Franques, Pierre Moreau, Camille Evrard, Arnaud Chong-Si-Tsaon, Éric Frouin, Marie-Luce Auriault, Valérie Moulin, Audelaure Junca, Julie Godet, Lucie Lebeau, Roxane Aguillon, Gaëlle Tachon, Lucie Karayan-Tapon, David Tougeron","doi":"10.1177/17562848251347375","DOIUrl":null,"url":null,"abstract":"Background: Colorectal cancers (CRC) with deficient mismatch repair system and/or microsatellite instability-high (dMMR/MSI-H) phenotype represent about 12% of CRC. dMMR/MSI-H CRC is due to a germline mutation (Lynch syndrome, LS) or an age-related epigenetic mechanism, mostly by hypermethylation of MLH1 promoter (sporadic cases). It is well recognized that patients with LS have a high lifetime risk of various dMMR/MSI-H cancers, but there are no data concerning the risk of a second cancer in sporadic dMMR/MSI-H CRC.Objectives: The main objective of this study was to determine the risk of having another primary cancer (APC) in patients with dMMR/MSI-H CRC. We also collected these tumors to determine their MMR phenotype.Design: We used a prospective cohort of 484 well-characterized patients with dMMR/MSI-H CRC to describe their risk of having APC.Methods: We evaluated the occurrence of APC (before or after the occurrence of the dMMR/MSI-H CRC) according to LS versus sporadic status, whatever the stage or the tumor site. The characteristics of the two groups, with and without APC, and LS versus sporadic status were compared.Results: Among the 484 patients with dMMR/MSI-H CRC, we identified 116 patients with a previous or a second primary tumor (24.0%), with an average of 1.4 tumors per patient in addition to the dMMR/MSI-H CRC. The most frequent tumor sites were skin (24.7%) and breast (18.5%). Regarding the occurrence of APC, we found no difference between patients with LS-related dMMR/MSI-H CRC group (25.0%) and those with sporadic dMMR/MSI-H CRC (24.8%). No risk factor was associated with the occurrence of APC in our cohort, in the LS or sporadic cases subgroup. In the sporadic group, 3.8% of APC had a dMMR/MSI-H phenotype as compared to 50.0% in the LS group.Conclusion: It seems important to follow patients with a history of dMMR/MSI-H CRC due to the high risk of second tumors, even in sporadic cases. Second cancers in patients with sporadic dMMR/MSI-H CRC are rarely associated with a dMMR/MSI-H phenotype.","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":"18 ","pages":"17562848251347375"},"PeriodicalIF":3.4000,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182622/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562848251347375","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Colorectal cancers (CRC) with deficient mismatch repair system and/or microsatellite instability-high (dMMR/MSI-H) phenotype represent about 12% of CRC. dMMR/MSI-H CRC is due to a germline mutation (Lynch syndrome, LS) or an age-related epigenetic mechanism, mostly by hypermethylation of MLH1 promoter (sporadic cases). It is well recognized that patients with LS have a high lifetime risk of various dMMR/MSI-H cancers, but there are no data concerning the risk of a second cancer in sporadic dMMR/MSI-H CRC.

Objectives: The main objective of this study was to determine the risk of having another primary cancer (APC) in patients with dMMR/MSI-H CRC. We also collected these tumors to determine their MMR phenotype.

Design: We used a prospective cohort of 484 well-characterized patients with dMMR/MSI-H CRC to describe their risk of having APC.

Methods: We evaluated the occurrence of APC (before or after the occurrence of the dMMR/MSI-H CRC) according to LS versus sporadic status, whatever the stage or the tumor site. The characteristics of the two groups, with and without APC, and LS versus sporadic status were compared.

Results: Among the 484 patients with dMMR/MSI-H CRC, we identified 116 patients with a previous or a second primary tumor (24.0%), with an average of 1.4 tumors per patient in addition to the dMMR/MSI-H CRC. The most frequent tumor sites were skin (24.7%) and breast (18.5%). Regarding the occurrence of APC, we found no difference between patients with LS-related dMMR/MSI-H CRC group (25.0%) and those with sporadic dMMR/MSI-H CRC (24.8%). No risk factor was associated with the occurrence of APC in our cohort, in the LS or sporadic cases subgroup. In the sporadic group, 3.8% of APC had a dMMR/MSI-H phenotype as compared to 50.0% in the LS group.

Conclusion: It seems important to follow patients with a history of dMMR/MSI-H CRC due to the high risk of second tumors, even in sporadic cases. Second cancers in patients with sporadic dMMR/MSI-H CRC are rarely associated with a dMMR/MSI-H phenotype.

Abstract Image

查看原文本刊更多论文

错配修复系统/微卫星不稳定性缺陷患者的第二种恶性肿瘤——高结直肠癌。

背景：具有错配修复系统缺陷和/或微卫星不稳定性高（dMMR/MSI-H）表型的结直肠癌（CRC）约占CRC的12%。dMMR/MSI-H CRC是由于种系突变（Lynch综合征，LS）或年龄相关的表观遗传机制，主要是MLH1启动子的高甲基化（散发性病例）。众所周知，LS患者一生中患各种dMMR/MSI-H癌症的风险很高，但没有关于散发的dMMR/MSI-H CRC发生第二种癌症风险的数据。目的：本研究的主要目的是确定dMMR/MSI-H CRC患者发生另一原发癌（APC）的风险。我们还收集了这些肿瘤以确定其MMR表型。设计：我们使用了484例dMMR/MSI-H CRC患者的前瞻性队列来描述他们患APC的风险。方法：我们评估APC的发生（在dMMR/MSI-H CRC发生之前或之后），根据LS和散发性状态，无论分期或肿瘤部位。比较两组有APC和无APC、LS和散发状态的特点。结果：在484例dMMR/MSI-H CRC患者中，我们确定了116例既往或第二原发肿瘤患者（24.0%），除dMMR/MSI-H CRC外，平均每例患者1.4个肿瘤。最常见的肿瘤部位为皮肤（24.7%）和乳房（18.5%）。关于APC的发生，我们发现ls相关dMMR/MSI-H CRC组患者（25.0%）和散发dMMR/MSI-H CRC患者（24.8%）之间没有差异。在我们的队列中，在LS或散发病例亚组中，没有风险因素与APC的发生相关。在散发组中，3.8%的APC具有dMMR/MSI-H表型，而LS组为50.0%。结论：对有dMMR/MSI-H CRC病史的患者进行随访，即使是散发病例，也有较高的二次肿瘤风险。散发性dMMR/MSI-H CRC患者的第二种癌症很少与dMMR/MSI-H表型相关。

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

Therapeutic Advances in Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

6.70

自引率

2.40%

发文量

103

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area. The editors welcome original research articles across all areas of gastroenterology and hepatology. The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.