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

Prostate cancer (PCa) is a multifocal and heterogeneous disease. Genetic predisposition accounts for more than 50% of PCa risk. Missense single-nucleotide polymorphisms can influence disease susceptibility by altering protein structure, function, and regulatory interactions. Protein kinase C Zeta (PRKCZ) regulates various cellular pathways, and its aberrant expression is associated with cancer metastasis and chemoresistance. Genetic variations in PRKCZ may lead to cancer onset and progression. Moreover, current PCa testing modalities are limited in their ability to predict tumor heterogeneity and patient outcomes. Therefore, the current study aimed to determine the genetic association of the PRKCZ missense variant rs202071893 with PCa risk and progression. DNA was extracted from blood samples of PCa patients and healthy control individuals using the phenol-chloroform protocol. Hardy-Weinberg Equilibrium (HWE) was evaluated in the control group to assess genetic stability in the studied population. QUANTO was used to calculate the power of the current study. Genotyping was performed via mutation-specific Tetra-ARMS PCR. Multiple genetic models (allele, codominant, dominant, recessive, overdominant) were applied to comprehensively assess the association between rs202071893 and PCa risk and development. Statistical analyses, such as the chi-square and Fisher’s exact tests, were performed to assess the association of rs202071893 with PCa risk and clinical parameters, including tumor stage, metastasis, and family history. The raw p-values were adjusted using a Bonferroni correction to reduce Type 1 error from multiple comparisons. The genotype distribution in the control group conformed to HWE ( p = 0.4323). rs202071893 was significantly associated with increased PCa risk and development under the recessive (OR = 5.108, RR = 2.167, p < 0.0005) allele (OR = 2.652, RR = 1.666, p = 0.0075) and codominant models (OR = 3.654, RR = 2.754, p = 0.0025), indicating variant homozygous GG and variant allele G as risk genetic variations. However, heterozygous AG showed a significant protective effect under the overdominant genetic model (OR = 0.2404, RR = 0.4454, p < 0.0005). Moreover, a non-significant association in subgroup analysis may represent a type II error due to a small subgroup sample size following stratification. The study findings highlighted that rs202071893 could serve as a non-invasive genetic marker for PCa, offering novel insights into tumor biology and informing future therapeutic strategies against PCa.