Association of MUTYH mutations with breast cancer risk and adverse prognosis: a Chinese cohort study

Before this study, MUTYH’s established role was primarily in colorectal cancer syndromes, and large-scale evidence on its germline mutations in breast cancer—particularly among Chinese women—was absent, leaving its susceptibility contribution and clinical significance unclear.

This study provides the first large-scale evidence that germline heterozygous MUTYH mutations confer a nearly fourfold increased breast cancer risk in Chinese women and identifies a distinct clinical profile of human epidermal growth factor receptor 2-negative tumours, high multiple primary cancer rates and independently worse recurrence-free survival in carriers.

These findings support integrating MUTYH into genetic testing panels for high-risk Chinese patients with breast cancer, justify intensified surveillance for multiple primary malignancies in carriers and provide a clinical rationale for investigating MUTYH-targeted therapeutic strategies.