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

Background Large-scale studies on MUTYH germline mutations in breast cancer among Chinese women remain limited. This study aimed to systematically assess the role of MUTYH mutations in breast cancer susceptibility, clinicopathological features and prognosis in this population. Methods A total of 5516 patients with breast cancer and 575 healthy controls were enrolled for the case–control analysis of mutation frequency and risk estimation; a nested cohort of 109 MUTYH mutation carriers and 321 wild-type breast cancer controls was used for clinicopathological, family history and prognostic comparisons. Statistical analyses were performed to evaluate the association between MUTYH mutations and breast cancer risk as well as prognosis. Results MUTYH germline mutations were identified in 2.0% of patients with breast cancer, which was associated with a significantly increased breast cancer risk (OR=3.84, 95% CI 1.22 to 12.12, p=0.014). The c.934-2A>G variant accounted for 77.1% of all mutations. Clinically, MUTYH carriers predominantly exhibited human epidermal growth factor receptor 2-negative tumours (81.9% vs 64.8%) and were enriched in luminal A subtypes (27.6% vs 14.0%). Moreover, carriers showed elevated rates of multiple primary cancers (17.4%) and significant familial cancer aggregation (46.8%). Importantly, MUTYH mutation emerged as an independent adverse prognostic factor for recurrence/metastasis (adjusted HR=1.82, 95% CI 1.08 to 3.07, p=0.024). Conclusion These findings establish MUTYH as a susceptibility gene with distinct clinicopathological and prognostic implications in Chinese patients with breast cancer, supporting its integration into genetic testing protocols for high-risk individuals and highlighting the need for further mechanistic and therapeutic investigations.