LZTR1 – Breast Cancer

Emerging evidence suggests that heterozygous LZTR1 variants may confer increased breast cancer risk. A splice-site deletion, c.1260+1del, was identified in a 38-year-old woman with bilateral early-onset breast cancer, highlighting potential pathogenicity of loss-of-function alleles (PMID:40724954). In a meta-analysis of three whole-exome sequencing datasets comprising 26,368 female cases and 217,673 controls, rare protein-truncating and predicted-deleterious missense variants in LZTR1 showed a significant burden in breast cancer patients (P<1e-4) (PMID:37592023). No additional familial segregation data or quantitative risk estimates have been reported to date.

Functional studies directly assessing LZTR1’s role in breast tumorigenesis are currently lacking; mechanistic insights derive primarily from RAS-MAPK pathway research in other contexts. Further replication in independent cohorts, detailed segregation analyses, and tumor-based functional assays are needed to establish LZTR1 as a clinically actionable breast cancer susceptibility gene. Key take-home: Preliminary genetic data support LZTR1 as a candidate moderate-penetrance breast cancer gene, but conclusive clinical utility awaits robust validation.

References

• International journal of molecular sciences • 2025 • LZTR1: c.1260+1del Variant as a Significant Predictor of Early-Age Breast Cancer Development: Case Report Combined with In Silico Analysis. PMID:40724954
• Nature genetics • 2023 • Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk. PMID:37592023

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