Hereditary Gastrointestinal Tumor Syndromes - When Risk Comes with Your Genes

Sep 21, 2026

Upload by Noah

Gastrointestinal neoplasms remain among the most frequent and lethal cancers, even as screening efforts and molecular advances continue. Most cases are sporadic, yet established familial syndromes carry substantial risk for both benign and malignant GI tumors. Early clinical descriptions have been increasingly clarified through high-throughput molecular data, including next-generation sequencing that reveals high-risk genetic variants while some remain unknown. Genetic assessment and counseling can change management, but may also cause psychological distress, particularly for patients with indeterminate variants. The review summarizes key hereditary cancer syndromes affecting the stomach and colon, emphasizing new molecular findings, novel entities, and recent management updates.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

Introduction

Gastric Cancer

Familial and Hereditary Gastric Cancer

Review Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes María Jesús Fernández Aceñero 1,2, * and Cristina Díaz del Arco 1,2, * Citation: Fernández Aceñero, M.J.; Díaz del Arco, C. Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes. Curr. Issues Mol. Biol. 2024, 46, 6440–6471. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cimb46070385 Academic Editor: Golder N. Wilson Received: 27 May 2024 Revised: 19 June 2024 Accepted: 25 June 2024 Published: 26 June 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain 2 Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain * [Correspondence: jmariajesus.fernandez@salud.madrid.org](Correspondence: jmariajesus.fernandez@salud.madrid.org) (M.J.F.A.); [cristina.diaz@salud.madrid.org](cristina.diaz@salud.madrid.org) (C.D.d.A.) Abstract: Despite recent campaigns for screening and the latest advances in cancer therapy and molecular biology, gastrointestinal (GI) neoplasms remain among the most frequent and lethal human tumors. Most GI neoplasms are sporadic, but there are some well-known familial syndromes associated with a significant risk of developing both benign and malignant GI tumors. Although some of these entities were described more than a century ago based on clinical grounds, the increasing molecular information obtained with high-throughput techniques has shed light on the pathogenesis of several of them. The vast amount of information gained from next-generation sequencing has led to the identification of some high-risk genetic variants, although others remain to be discovered. The opportunity for genetic assessment and counseling in these families has dramatically changed the management of these syndromes, though it has also resulted in significant psychological distress for the affected patients, especially those with indeterminate variants. Herein, we aim to summarize the most relevant hereditary cancer syndromes involving the stomach and colon, with an emphasis on new molecular findings, novel entities, and recent changes in the management of these patients. Keywords: next-generation sequencing; familial syndromes; cancer; gastrointestinal tract; management; gastric cancer; colorectal cancer; genetic variant; mutation; hereditary 1. Introduction Despite recent campaigns for screening and the latest advances in therapy and molecular biology, gastrointestinal (GI) neoplasms remain among the most frequent and lethal human tumors [1] . Most GI neoplasms are sporadic, but there are some well-known familial syndromes associated with a predisposition to the development of GI cancer. The increasing use of next-generation sequencing (NGS) and revolutionary genetic technologies has led to the discovery of many new pathogenic or likely pathogenic variants of genes associated with GI and other human cancers [2] . The aim of this report is to review the genetic basis of both well-known syndromes and some of the most novel ones associated with gastric cancer (GC) and colorectal cancer (CRC), highlighting how this knowledge influences disease prevention and management. 2. Gastric Cancer GC is the fifth most common cancer and the fourth leading cause of cancer-related deaths worldwide [3] . Its incidence varies geographically, being higher in Asian countries and lower in Western countries, where it is often diagnosed at advanced stages and has a five

FAQs

Why do gastrointestinal cancers remain a major clinical challenge despite recent advances?

Gastrointestinal neoplasms remain among the most frequent and lethal human tumors, even with ongoing screening campaigns and therapeutic and molecular biology advances.

How do molecular techniques like next-generation sequencing contribute to understanding hereditary GI tumors?

High-throughput and next-generation sequencing have identified high-risk genetic variants for several hereditary syndromes, while other variants are still being discovered.

What impact does genetic assessment and counseling have for patients with hereditary syndromes?

Genetic assessment and counseling can dramatically change management, but it can also lead to significant psychological distress, especially for patients with indeterminate variants.

Sep 21, 2026

Upload by Noah