PCSK9 rs562556 variant and survival in BRCA1 mutation carriers and mutation-negative familial breast cancer

Breast cancer etiology involves a complex interplay of various risk factors, with genetic alterations playing a significant role in susceptibility to the disease. While mutations in genes such as BRCA1 and BRCA2 are well established in elevating breast cancer risk, their potential role in predicting metastatic progression remains unclear. A recent study by Mei et al. suggested that a common germline variant in the PCSK9 gene (rs562556) may increase metastasis risk and lower survival rates in breast cancer patients. To investigate this association, we evaluated the relationship between the PCSK9 rs562556 variant genotypes and survival outcomes in two cohorts: patients with BRCA1 mutations and those with familial breast cancer lacking mutations in known susceptibility genes. Our study included 1052 BRCA1 mutation carriers, 467 familial breast cancer patients of unknown genetic etiology, and 1404 controls. Genotyping was performed using TaqMan genotyping and whole-exome sequencing. Survival analyses were conducted using Kaplan-Meier survival curves and Cox proportional hazards models. We found no significant association between PCSK9 rs562556 variant and breast cancer mortality or time to death following distant recurrence in either cohort. This finding does not support PCSK9 prognostic impact in breast cancer that may be modified by additional genetic or environmental factors.