A genetic association study has identified the PRKCZ missense variant rs202071893 as a significant factor in prostate cancer susceptibility, demonstrating strong links to disease risk across multiple genetic models and highlighting its potential as a non-invasive biomarker.

Prostate cancer is recognized as a multifocal and heterogeneous disease in which genetic predisposition contributes to more than 50 percent of overall risk. Missense single-nucleotide polymorphisms can alter protein structure, function, and regulatory interactions, thereby modifying susceptibility to malignancy. Protein kinase C Zeta (PRKCZ) participates in multiple cellular pathways, and its aberrant expression has previously been implicated in cancer metastasis and chemoresistance, suggesting that inherited variations in the gene could promote cancer onset and progression while addressing limitations in current testing modalities.

To evaluate the relationship between rs202071893 and disease susceptibility, investigators isolated genomic DNA from blood samples of prostate cancer patients and healthy control subjects using a phenol-chloroform extraction protocol. Genotyping was conducted via mutation-specific Tetra-ARMS PCR. Study statistical power was evaluated using QUANTO software, and the control cohort was assessed for Hardy-Weinberg Equilibrium to verify genetic stability within the study population.

The genotype distribution among healthy controls conformed to Hardy-Weinberg Equilibrium with a p-value of 0.4323. Comprehensive evaluation across multiple inheritance models demonstrated that rs202071893 was significantly associated with elevated prostate cancer risk under the recessive model (odds ratio = 5.108, relative risk = 2.167, p < 0.0005), the codominant model (odds ratio = 3.654, relative risk = 2.754, p = 0.0025), and the allele model (odds ratio = 2.652, relative risk = 1.666, p = 0.0075), establishing the homozygous GG genotype and the G allele as risk-conferring variations.

In contrast to the risk observed with the homozygous variant, the heterozygous AG genotype exhibited a statistically significant protective effect under an overdominant genetic model, yielding an odds ratio of 0.2404 and a relative risk of 0.4454 (p < 0.0005). Researchers also conducted statistical analyses using chi-square and Fisher’s exact tests to evaluate relationships between the variant and clinical parameters such as tumor stage, metastasis, and family history, applying Bonferroni corrections to raw p-values to control for Type I errors.

Subgroup analyses stratified by clinical characteristics yielded non-significant associations, which the authors noted may reflect Type II error resulting from reduced sample sizes within stratified groups. Overall, the researchers reported that rs202071893 holds promise as a non-invasive genetic marker for prostate cancer, providing biological insights into tumor characteristics and informing future therapeutic strategies.

Subject of Research: Genetic association of the PRKCZ missense variant rs202071893 with prostate cancer risk

Article Title: PRKCZ missense variant rs202071893 as a potential genetic marker for prostate cancer

Article References: Nadeem, L., Chishti, U. K., Mustafa, A., Shabbir, M., Badshah, Y., Trembley, J. H., Afsar, T., Ashraf, N. M., Aldisi, D., & Razak, S. (2026). PRKCZ missense variant rs202071893 as a potential genetic marker for prostate cancer. Discover Oncology. https://doi.org/10.1007/s12672-026-06142-2

Image Credits: AI Generated

DOI: 10.1007/s12672-026-06142-2

Keywords: PRKCZ, rs202071893, prostate cancer, missense variant, protein kinase C zeta, Tetra-ARMS PCR, Hardy-Weinberg equilibrium, single-nucleotide polymorphisms, recessive model, codominant model, overdominant model, allele model, QUANTO, Bonferroni correction, tumor heterogeneity, chemoresistance, cancer metastasis