MUTYH – Hereditary Breast Carcinoma

Several multi-gene panel studies have reported heterozygous MUTYH variants among breast cancer cohorts but without evidence of causality. In a Bahraini series of 54 familial breast cancer cases, one patient carried the c.1187G>A (p.Gly396Asp) variant (1.85 %) (PMID:37656691). A larger retrospective analysis of 3 598 patients, including 766 with breast cancer, found 14 MUTYH carriers (1.8 %) versus 1.5 % in non-breast populations (p = 0.49) and no significant enrichment (PMID:38254803). No segregation data or functional assays in breast tissue have been reported to support a role for monoallelic MUTYH defects in breast carcinogenesis.

Given the absence of reproducible familial segregation, the low and non-significant carrier frequency in breast cancer cases, and lack of tissue-specific functional evidence, the gene–disease association is considered disputed. Routine clinical testing of MUTYH for hereditary breast carcinoma is not supported outside its established role in MUTYH-associated polyposis. Key take-home: current data do not justify inclusion of MUTYH in hereditary breast cancer testing panels.

References

• Cancer Genet. • 2023 • MUTYH has conflicting data regarding its relationship to hereditary breast cancer PMID:38254803
• Int. J. Cancer. • 2023 • Next-generation sequencing in Bahraini women with breast cancer reveals monoallelic MUTYH variant PMID:37656691

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