Abstract

Background: Lynch syndrome (LS) accounts for 3–5% of colorectal cancers and is
characterized by mismatch repair (MMR) deficiency and microsatellite instability (MSI),
leading to accelerated tumorigenesis¹–³. Latin American data remain limited.
Aim: To characterize the clinical, endoscopic, histopathological, and molecular features of
LS-associated colorectal cancer (CRC) in a Mexican tertiary referral center.
Methods: This retrospective cohort included 36 patients with confirmed LS-associated
CRC identified within a registry of 117 individuals under LS surveillance. Clinical,
endoscopic, histologic, molecular, and oncologic outcomes were analyzed descriptively.
Results: Mean age at CRC diagnosis was 42.9 years. Right-sided tumors predominated
(58.3%). Common presentations included bleeding (66.7%) and anemia (66.7%). Most
tumors were moderately differentiated adenocarcinomas; mucinous histology was present
in 27.8%. dMMR was observed in 63.9%, MSI in 61.1%. MLH1 was the most frequent
germline variant (58.3%). Extracolonic malignancies were documented in 47.2% of the
overall Lynch syndrome cohort and in 36.1% of LS-CRC patients; additionally, 27.8% of
LS-CRC patients developed metachronous CRC. Only one LS-related death occurred.
Conclusion: LS-associated CRC in this cohort exhibited early onset, right-sided
predominance, high MSI/dMMR rates, and high metachronous and extracolonic cancer
burden. These findings support intensified surveillance and genetic evaluation in LS
populations.

Keywords

Lynch syndrome, colorectal cancer, mismatch repair deficiency, microsatellite instability, hereditary cancer, Mexico