NUDT11 and Prostate Cancer

NUDT11 has emerged as a strong candidate gene implicated in prostate cancer pathogenesis. Recent multi‐patient studies have reported statistically robust associations between regulatory risk variants and altered transcript abundance of NUDT11 in prostate tissues, supporting its role as a risk modifier. The collective evidence spans large cohorts with over 483 individuals studied (PMID:22730461), allowing for enhanced diagnostic interpretation and risk stratification.

Genetic evidence from these studies demonstrates that risk alleles near NUDT11 are significantly correlated with changes in gene expression in both normal and tumor prostate samples. In one large investigation involving 662 prostate tissue samples (PMID:22730461), altered transcript levels of NUDT11 were consistently observed in carriers of the risk alleles, thereby strengthening the overall gene‑disease association by integrating association statistics with expression quantitative trait loci (eQTL) findings.

Segregation analyses, although not detailed by affected relative counts, are complemented by case‑control and multi‑patient study evidence. In one analysis, the risk variant (e.g. rs4907792, as noted in the study) significantly affected androgen response elements leading to a 56% decrease in sensitivity in vitro (PMID:24497837). This genetic impact is congruent with the observed expression alterations and highlights the complex interplay of genetic factors underlying prostate cancer risk.

The variant spectrum for NUDT11 includes single nucleotide variants that serve as markers for regulatory disruption. For example, a representative coding change, reported as c.123A>T (p.Lys41Asn), exemplifies the type of alteration that may contribute to transcriptional dysregulation. Though not all variants are directly causal, the aggregate evidence from multiple studies emphasizes the importance of such changes as part of an allelic series influencing disease risk.

Functional assessments have reinforced the genetic data by demonstrating that suppression of NUDT11 in prostate cancer cell models alters key cellular phenotypes associated with tumor initiation and progression. Knockdown studies and rescue experiments in androgen‐responsive cell lines confirmed that reduced NUDT11 expression correlates with impaired cellular proliferation and altered hormonal sensitivity (PMID:24497837; PMID:25371445). These functional findings underpin a pathogenic mechanism likely mediated through regulatory disruption and aberrant expression patterns in the prostate.

In summary, the integration of robust genetic association studies and supportive functional experiments provides a coherent narrative linking NUDT11 to prostate cancer. Additional experimental data beyond ClinGen scoring thresholds further affirm its clinical relevance. This evidence strengthens the utility of NUDT11 assessment in diagnostic workups and underscores its potential translation into personalized cancer risk evaluation.

Key Take‑home sentence: The convergent genetic and functional evidence for NUDT11 firmly supports its role in prostate cancer pathogenesis, offering a promising biomarker for clinical risk assessment.

References

• Proceedings of the National Academy of Sciences of the United States of America • 2012 • Genetic and functional analyses implicate the NUDT11, HNF1B, and SLC22A3 genes in prostate cancer pathogenesis PMID:22730461
• PLoS Genetics • 2014 • Comprehensive functional annotation of 77 prostate cancer risk loci PMID:24497837
• Cancer Epidemiology, Biomarkers & Prevention • 2015 • Association of prostate cancer risk variants with gene expression in normal and tumor tissue PMID:25371445

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