MBD2 – Breast Cancer Risk

MBD2 (HGNC:6917) is implicated in modulating the risk of breast cancer (MONDO_0007254) through its role in epigenetic regulation. The protein encoded by MBD2 binds methylated DNA and functions as a transcriptional regulator, suggesting that alterations in its activity may influence carcinogenic processes. This association has been explored in multiple independent case‑control studies.

One study evaluated 393 breast cancer cases and matched controls in a Connecticut cohort, demonstrating that noncoding SNPs in MBD2 were significantly associated with reduced breast cancer risk in premenopausal women (PMID:16168120). A subsequent investigation involving 2,795 cases and 4,505 controls from Alberta further supported the association by identifying SNP‑SNP interactions among genes involved in DNA repair, modification, and metabolism that included MBD2 (PMID:23755158).

The genetic evidence for MBD2 in breast cancer is bolstered by the statistically significant associations observed in these large cohorts. Although no specific coding HGVS variant was reported, the correlation noted for SNPs affecting regulatory regions supports a moderate level of genetic evidence. This is reflective of the complex genetic architecture common to breast cancer susceptibility.

Functional studies provide additional, albeit limited, context. Assays measuring the binding affinity of MBD2 for methylated DNA report high‐affinity interactions (PMID:26384511), implying a mechanistic basis in epigenetic regulation that could underlie the observed genetic associations. However, direct experimental validation in breast tissue remains to be established.

While current evidence from case‑control studies and supporting biochemical assays underpin a moderate gene–disease association, limitations such as the absence of familial segregation data and lack of coding variant analysis should be addressed in future investigations. The integration of genetic and functional data highlights the potential of MBD2 as a biomarker for breast cancer risk, particularly in premenopausal women.

Key take‑home sentence: The combined genetic association and supportive functional data indicate that MBD2 plays a moderate yet clinically meaningful role in breast cancer risk assessment, meriting further exploration as a potential biomarker for targeted risk stratification.

References

• Breast cancer research : BCR • 2005 • Genotypes and haplotypes of the methyl-CpG-binding domain 2 modify breast cancer risk dependent upon menopausal status PMID:16168120
• PloS one • 2014 • Assessing SNP-SNP interactions among DNA repair, modification and metabolism related pathway genes in breast cancer susceptibility PMID:23755158
• Protein engineering, design & selection : PEDS • 2015 • Characterization and directed evolution of a methyl-binding domain protein for high-sensitivity DNA methylation analysis PMID:26384511

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