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The association between H2BC15 and prostate cancer has been highlighted by two independent transcriptome-wide association studies. In these studies, genetically predicted expression of H2BC15 was significantly associated with prostate-specific antigen (PSA) levels in a large cohort of 95,768 PCa‐free men (PMID:37205487) and further replicated in an independent cohort of 209,318 individuals (PMID:38845201). This robust sample size and consistency between studies provide a solid quantitative foundation to the association, although they reflect statistical correlations rather than classical Mendelian segregation.
Genetic evidence supporting this association is derived from the TWAS framework that identifies genes impacting PSA levels, a key biomarker for prostate cancer screening. No individual coding variants were reported in these studies for H2BC15; rather, significant associations were based on tissue-specific gene expression patterns. Despite the lack of traditional variant evidence such as missense or loss‐of‐function changes, the high statistical significance across independent datasets lends credence to the gene’s involvement.
Functional assessments remain limited, yet preliminary insights indicate that H2BC15, as a histone-related gene, may play a role in chromatin remodeling in prostate tissue. Although direct functional experiments were not detailed, the implication of epigenetic mechanisms provides a plausible biological rationale connecting H2BC15 expression with altered PSA levels. Additional mechanistic studies would be required to fully delineate its role in prostate carcinogenesis.
There is currently no study presenting conflicting evidence that disputes the association between H2BC15 and prostate cancer. Nonetheless, the fact that both studies focused on PSA levels in men without diagnosed prostate cancer suggests that the association might reflect a contribution to risk modulation rather than a classic monogenic pathogenic mechanism.
Integrating the genetic and preliminary functional observations, the current evidence supports a moderate degree of association between H2BC15 and prostate cancer. These findings offer a promising direction for future investigations and potential clinical utility in risk assessment and early screening where gene expression profiles could complement existing diagnostic methods.
Key Take‑home Message: While further functional validation is needed, the reproducible TWAS signals from large, independent datasets substantiate H2BC15 as a candidate gene for prostate cancer risk, supporting its potential incorporation in diagnostic and commercial screening strategies.
Gene–Disease AssociationModerateLarge TWAS sample sizes (95,768 [PMID:37205487] and replication in 209,318 [PMID:38845201]) and consistent statistical association support a moderate gene‑disease association despite the absence of segregation data. Genetic EvidenceModerateTWAS analyses identified statistically significant associations for H2BC15 in two independent cohorts, providing reproducible genetic evidence even though no discrete coding variants were reported. Functional EvidenceLimitedLimited experimental data exist; however, the known role of histone genes in chromatin remodeling offers a plausible, though not yet fully validated, mechanism for prostate cancer susceptibility. |