KLK14 – Prostate Cancer

KLK14 has emerged as a significant genetic marker in prostate cancer, with evidence supporting its role in modulating tumour aggressiveness. Recent multi‑patient studies have assessed common genetic variants within the KLK14 locus in cohorts exceeding 1200 cases (PMID:22505522). These investigations provide a strong foundation for considering KLK14 as a prognostic marker in this malignancy.

The genetic evidence highlights three single nucleotide polymorphisms, including a recurrent missense variant. In particular, the variant c.97G>A (p.Gln33Arg) has been associated with higher Gleason scores and aggressive disease features in prostate cancer patients (PMID:22505522). Although the studies do not report extended familial segregation, the strong statistical associations across large case–control cohorts underpin the clinical relevance of KLK14 in prostate tumorigenesis.

Functionally, in vitro experiments have demonstrated that KLK14 is inversely regulated by androgen receptor signalling, a pattern distinct from other prostatic kallikreins. This regulatory mechanism is consistent with the aggressive tumour phenotypes observed and supports the hypothesis that altered KLK14 expression contributes to prostate cancer progression (PMID:22505522).

In addition to the direct genetic association, replication of these findings in independent cohorts lends further credence to the role of KLK14 as an important genetic factor. The combined genetic and functional evidence supports a strong link between KLK14 and prostate cancer, even though classical familial segregation data are limited.

The collective findings suggest that KLK14 not only serves as a significant marker associated with prostate cancer aggressiveness but also offers potential utility in stratifying patients based on risk. Such integration of molecular data into clinical practice paves the way for more targeted management strategies.

Key Take‑Home: The robust association of KLK14 with aggressive prostate cancer, supported by both genetic and functional evidence, reinforces its clinical utility as a prognostic marker and a candidate for further therapeutic targeting.

References

• Biological Chemistry • 2012 • The kallikrein 14 gene is down‑regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness PMID:22505522
• Annals of Oncology • 2018 • MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer PMID:29509840

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