Lynch syndrome and colorectal cancer - A review of current perspectives in molecular genetics and clinical strategies

Sep 23, 2026

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Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is an inherited condition that substantially increases lifetime risk of colorectal cancer (CRC) and other malignancies. It results from germline mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2), causing microsatellite instability and defective DNA repair. Early detection and structured prevention rely on endoscopic surveillance, especially regular colonoscopy, and universal screening for MMR deficiency. Genetic counseling supports informed decisions and reproductive options.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Molecular Genetics

DNA mismatch repair mechanism

Germline risk, surveillance, and screening

Genetic counseling and clinical strategies

ONCOLOGY RESEARCH 2025 33(7): 1531-1545 REVIEW Lynch syndrome and colorectal cancer: A review of current perspectives in molecular genetics and clinical strategies RAQUEL GÓMEZ-MOLINA 1,*; RAQUEL MARTÍNEZ2,3,4; MIGUEL SUÁREZ2,3,4,*; ANA PEÑA-CABIA 1; MARÍA CONCEPCIÓN CALDERÓN 1; JORGE MATEO3,4 1 Department of Laboratory Medicine, Virgen de la Luz Hospital, Cuenca, 16002, Spain 2 Gastroenterology Department, Virgen de la Luz Hospital, Cuenca, 16002, Spain 3 Medical Analysis Expert Group, Institute of Technology, Universidad de Castilla-La Mancha, Cuenca, 16071, Spain 4 Medical Analysis Expert Group, Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, 45071, Spain Key words: Lynch Syndrome (LS), Colorectal Cancer (CRC), Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Genetic testing, DNA Mismatch Repair (MMR), Endoscopy, Colonoscopy, Genetic counseling Abstract: Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is an inherited condition associated with a higher risk of colorectal cancer (CRC) and other cancers. It is caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6 and PMS2 . These mutations lead to microsatellite instability (MSI) and defective DNA repair mechanisms, resulting in increased cancer risk. Early detection of LS is crucial for effective management and cancer prevention. Endoscopic surveillance, particularly regular colonoscopy, is recommended for individuals with LS to detect CRC at early stages. Additionally, universal screening of CRC for MMR deﬁciency can help identify at-risk individuals. Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis, making informed decisions regarding surveillance and prevention, and offering reproductive options to reduce the transmission of pathogenic variants of the offspring. The aim of this review is to outline current strategies for the diagnosis, surveillance, and management of LS, with a focus on the role of genetic counseling, endoscopic screening, and emerging therapeutic approaches to mitigate cancer risk in affected individuals. Introduction Lynch Syndrome (LS) is associated with a signiﬁcantly increased lifetime risk of developing colorectal cancer (CRC), with estimates ranging from 30% to 74% depending on germline pathogenic variant [1–3] . LS is the most common heritable CRC syndrome, with an estimated prevalence of 1 in 440 in the general population [4,5] . The syndrome also increases the risk of several other malignancies, such as those of the cancer of stomach, small intestine, pancreas, biliary tract, urinary tract, brain and skin [2,4,6] . Women with LS have a particularly high risk of endometrial and ovarian cancers [7] . Approximately 20% of *Address correspondence to: Raquel Gómez-Molina, rgomezmolina@sescam.jccm.es; Miguel Suárez, msuarezmatias@sescam.jccm.es Received: 30 January 2025; Accepted: 21 April 2025; Published: 26 June 2025 CRC patients have at least one ﬁrst-degree relative with a history of this cancer [8,9] . It is recommended that individuals with LS undergo regular surveillance, including colonoscopy every 1–2 years starting in their twenties, to detect and manage CRC early [10, 11] . Genetic testing and family history are essential for diagnosing LS and universal genetic testing of colorectal cancers is increasingly used to identify high-risk individuals [12] . Genetic counseling offers additional beneﬁts by helping patients and their families make informed decisions, providing tailored recommendations for personalized management, surveillance and prevention strategies, and presenting reproductive options to reduce the transmission of pathogenic variants to future generations [13] . Molecular Genetics LS or hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary CRC, accounting for 2%–4% of cases [9] . It is an aut

FAQs

What causes Lynch syndrome and how does it increase colorectal cancer risk?

Lynch syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6 and PMS2. These mutations lead to microsatellite instability and impaired DNA repair, increasing cancer risk.

Why is endoscopic surveillance important for people with Lynch syndrome?

Regular endoscopic surveillance, particularly colonoscopy at recommended intervals, helps detect colorectal cancer early stages. Early detection improves management and supports cancer prevention strategies.

How does genetic counseling contribute to Lynch syndrome management?

Genetic counseling guides patients and families in understanding the genetic basis of LS. It supports informed decisions about surveillance and prevention and offers reproductive options to reduce transmission of pathogenic variants.

Sep 23, 2026

Uploaded by Putri