Missense variants in PRKCD: elucidating their potential association with breast cancer.

Background: Missense single-nucleotide polymorphisms (SNPs) in various genetic pathways can lead to the development of breast cancer. Protein kinase C delta (PRKCD) is involved in various important cellular pathways, and its altered expression has been identified in different cancers. Genetic alteration in this gene can be involved in cancer onset and progression. To date, there are no studies performed to elucidate the role of PRKCD missense variants in the development of breast cancer. Therefore, this study aims to identify the association of pathogenic missense SNPs in PRKCD with breast cancer.

Methods: The missense variants of PRKCD were retrieved from the Ensembl and dbSNP databases. Missense variants were analysed through various computational tools, and four variants of PRKCD rs1703806197 (T/C), rs782555227 (G/A), rs1703449438 (T/C), and rs1575535582 (T/G) were selected from the data. The genotype analysis for these variants was performed for 360 breast cancer patients and 363 healthy controls. Statistical association of variants with breast cancer clinical features was determined through chi-square/Fisher's exact test with a significant P value ≤ 0.05 using GraphPad Prism 8.0 software.

Results: Genotype analysis of PRKCD variants showed that missense SNPs rs782555227 (G/A), rs1703449438 (T/C), and rs1575535582 (T/G) were associated with breast cancer (P value < 0.05). Furthermore, genotypes in these SNPs were also found to be associated with various clinical features of breast cancer patients. Genotypes AG, TC, and TT in variants rs782555227, rs1703449438, and rs1575535582, respectively, were associated with breast cancer metastasis. While genotype AG of variant rs782555227 was also found to be associated with menopausal status and hereditary breast cancer. Moreover, genotype TT in variant rs1575535582 was associated with BRCA1 positive status among the breast cancer patients.

Conclusion: The present study identified for the first time the association of specific PRKCD missense variants with breast cancer. These variants could be developed into possible genetic markers for the diagnosis of breast cancer at an early stage; however, further validation studies with a multiethnic large cohort size are required. Furthermore, functional studies of these variants will also aid in attaining insight into the molecular mechanisms through which these missense variants are involved in breast cancer.