DNPH1 – Breast Cancer

The association between DNPH1 and breast cancer has been evaluated using large‐scale proteomic and Mendelian randomization approaches. Two independent studies have demonstrated significant associations between cis‐acting protein quantitative trait loci affecting DNPH1 levels and breast cancer risk (PMID:37996402), and these findings were replicated in a second cohort encompassing over 133,384 cases (PMID:39351539). Such consistency across independent multi‐patient studies supports a strong gene–disease association.

Genetic evidence for DNPH1 derives from analyses of circulating plasma proteins where cis‐acting variants were used as instruments to predict protein levels. Although no individual DNPH1 variants have been explicitly detailed in these reports, the genetic results provide moderate support based on tier‐three evidence in one study, with confirmatory results observed in the parallel independent analysis. No segregation data (i.e. affected relatives with the variant) were provided, which limits a family‐based assessment but does not detract from the overall statistical associations.

The inheritance mode associated with this risk factor is best conceptualized as autosomal dominant in nature, reflecting the fact that risk alleles for breast cancer are typically transmitted in a dominant pattern. The gene–disease association is underpinned by large-scale, population‐based analyses rather than traditional Mendelian segregation studies. As such, the genetic evidence primarily stems from common variants with small effect sizes that collectively modify disease risk.

Functional evidence in this context remains limited. There are currently no detailed in vitro or in vivo studies that functionally validate the effect of DNPH1 protein changes on oncogenic pathways. However, the proposed mechanism is that altered DNPH1 levels may disrupt cellular processes involved in tumor development, a hypothesis that is consistent with the biomarker profile observed in the studied cohorts.

No conflicting studies have been reported that refute the association, and the convergence of results across two high-powered studies lends substantial credibility to DNPH1 as a potential biomarker for breast cancer risk. Nonetheless, further experimental validation is necessary to elucidate the precise biological mechanisms by which DNPH1 contributes to carcinogenesis.

Key Take‑home: DNPH1 represents a promising biomarker for breast cancer risk prediction, warranting further functional studies to clarify its mechanistic role in tumorigenesis.

References

• Nature Communications • 2023 • Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation PMID:37996402
• Frontiers in Endocrinology • 2024 • Identifying new biomarkers and potential therapeutic targets for breast cancer through the integration of human plasma proteomics: a Mendelian randomization study and colocalization analysis PMID:39351539

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