Prevalence of MUTYH Monoallelic Variants in Patients With Hereditary Cancer Using Multigene Panel Testing

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• The MUTYH gene is crucial for DNA repair.
• Pathogenic variants (PVs) in MUTYH cause MUTYH-associated polyposis (MAP), increasing colorectal cancer (CRC) risk.
• Monoallelic MUTYH PVs may also elevate cancer risk, particularly for CRC and breast cancer (BC).

Purpose of the Study:

• To investigate the role of MUTYH gene variants in hereditary cancer.
• To compare MUTYH mutation frequencies in cancer patients versus healthy individuals.
• To analyze the clinical features and genetic profiles of patients with MUTYH PVs and their relatives.

Main Methods:

• Analyzed MUTYH status in 130 patients from a familial cancer clinic.
• Compared MUTYH mutation rates between the cancer cohort and 150 healthy volunteers.
• Described mutations, clinical features, and family genetic profiles.

Main Results:

• 10% of cancer patients carried a MUTYH PV, compared to 0% in controls.
• The most common PVs were c.1187G>A (p.Gly396Asp) and c.536A>G (p.Tyr179cys).
• Six patients had double mutations (DM), with some involving other cancer susceptibility genes.

Conclusions:

• A higher MUTYH mutation rate in cancer patients suggests a role in cancer predisposition.
• Cancer recurrence in heterozygous carriers and family branches with DMs indicates monoallelic PVs may contribute to cancer.
• MUTYH PVs might play a role in cancer predisposition and progression, even in the absence of MAP.