Non- synonymous single nucleotide polymorphisms (nsSNPs) impact disease onset and progression. Protein kinase C zeta (PRKCZ) is involved in oncological, neurological, and diabetes pathogenesis. The goal of the research presented here was to investigate the role of nsSNPs in PRKCZ in breast cancer (BC) pathogenesis.

Genotyping analysis was performed to determine the association of PRKCZ genetic variants rs1236161858 (G/T), rs367917640 (G/A/C), rs202071893(A/G), and rs757469768(G/A) with BC risk and clinicopathological variables through Tetra-ARMS PCR.

rs1236161858(G/T) was linked to higher BC risk in codominant (OR = 5.227, RR = 2.225), allele model, (OR = 4.701, and RR = 2.186) and log additive (OR = 2.564). rs367917640 (G/A) was associated with increased BC risk in codominant model (OR = 6.419, RR = 2.350), recessive model (OR = 12.09 and, RR = 4.772) and log additive (OR = 3.340). rs367917640(G/C) was linked to higher BC risk in dominant (OR = 4.892, RR = 2.208), recessive (OR = 1.859, RR = 1.34), over dominant (OR = 3.675, RR = 2.028) and log additive (1.579) models respectively. For rs202071893(A/G) codominant model (OR = 2.295 RR = 1.547), dominant model (OR = 5.943, and RR = 1.781) and over dominant model (OR = 3.433, and RR = 1.974) showed significantly higher BC association. rs757469768(G/A) was linked to higher BC risk in both dominant (OR = 0.1479, and RR = 0.4688) and over dominant (OR = 2.005, and RR = 1.455) models. However, rs757469768(G/A) was associated with reduced BC risk in log additive model (OR = 0.4956).rs1236161858 correlated with DCIS and IDC. rs367917640(G/A/C) correlated with early cancer stage, LCIS, DCIS, IDC, luminal A and post-menopause. rs202071893 was associated with HER2⁺and IDC. rs757469768 was not associated with clinicopathological features and risk factors.

All five nsSNPs exhibited potential as predictive and prognostic biomarkers for BC. However, the current study findings should be validated by conducting research on large cohorts with representation from diverse population. Furthermore, biological mechanism by which these nsSNPs cause BC pathogenesis could be explored in future studies.