Akademik Veri Yönetim Sistemi
2nd International Hereditary Cancer Congress, Antalya, Türkiye, 5 - 08 Şubat 2026, ss.22, (Özet Bildiri)
Objective: The MUTYH gene encodes a key enzyme of the base excision repair pathway and plays a critical role in maintaining genomic integrity by correcting oxidative DNA damage. Biallelic pathogenic variants in MUTYH are a well-established cause of MUTYH-associated polyposis, conferring a markedly increased lifetime risk of colorectal cancer. In contrast, the clinical relevance of monoallelic MUTYH pathogenic variants remains uncertain. Although heterozygous MUTYH variants are relatively common in the general population, their contribution to cancer susceptibility,particularly breast cancer has not been clearly defined. Previous studies have reported inconsistent and sometimes conflicting results, highlighting the need for further evaluation in large and well-characterized hereditary cancer cohorts. Materials-Methods: This retrospective study included 1,905 consecutive patients referred to our clinic for hereditary cancer evaluation between 2018 and 2025. All individuals underwent germline genetic testing using a 35 gene hereditary cancer panel based on next-generation sequencing. Detected variants were interpreted and classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Patients harboring pathogenic or likely pathogenic MUTYH variants were identified retrospectively. Demographic and clinical data were reviewed, and patients were stratified according to cancer diagnosis, with a particular focus on breast cancer. Results: Pathogenic or likely pathogenic MUTYH variants were identified in 51 of the 1,905 patients (2.7%). Among these individuals, 9 carried biallelic variants, while 42 were monoallelic carriers, corresponding to a monoallelic carrier frequency of approximately 2.2% in the overall cohort. Breast cancer was the most common malignancy, diagnosed in 1,042 patients. Within this subgroup, 18 individuals were monoallelic MUTYH pathogenic variant carriers, yielding a carrier frequency of 1.7% among breast cancer patients. Monoallelic MUTYH carriers were also observed across a variety of non-breast tumor types, supporting a broad tumor spectrum. Discussion: The role of monoallelic MUTYH variants in cancer susceptibility remains controversial. While current evidence does not support a strong, independent increase in breast cancer risk attributable to heterozygous MUTYH variants, their recurrent identification in patients with diverse malignancies suggests a potential biological relevance beyond colorectal cancer. Notably, the presence of monoallelic MUTYH variants in patients with a positive family history of cancer, cancer recurrence, or co-occurrence with other cancer susceptibility genes supports the hypothesis that heterozygous MUTYH variants may function as low-penetrance modifiers of cancer risk rather than classical high-penetrance predisposition genes. Conclusion: These results underscore the importance of cautious interpretation of MUTYH findings in multigene panel testing and emphasize the need for large, multicenter, and prospective studies to better define cancer risks and guide clinical management of monoallelic MUTYH carriers.