PDCD1 gene single nucleotide polymorphisms and haplotypes are associated with higher risk of breast cancer development

Introduction The programmed cell death protein 1 (PD-1), expressed mainly by T lymphocytes, is an important checkpoint of the immune response and may contribute to tumorigenesis when associated with its ligands, PD-L1 or PD-L2, expressed by tumor cells. In this context, this study aimed to analyze the allelic variants rs11568821 G>A and rs41386349 C>T of the PDCD1 gene in breast cancer patients and cancer-free women and correlate them with clinical-pathological parameters. Materials and methods DNA extraction was performed from peripheral blood samples and the PDCD1 genotyping was carried out by the polymerase chain reaction technique followed by enzymatic restriction (PCR-RFLP), the fragments were separated by acrylamide gel electrophoresis for genotyping. Results In this case-control association study, it was found that carriers of the A allele of the PDCD1 rs11568821 G>A genetic polymorphism have a higher risk of developing breast cancer (OR = 2.42; CI 95% = 1.59 - 3.69; p <0.001). This polymorphism was also correlated with positivity for estrogen (ER) (τ = 0.25; p <0.001) and progesterone (PR) receptors (τ = 0.17; p = 0.021). The haplotypic analysis also indicated that AC allele carriers have a higher risk of breast cancer development (OR = 2.41; CI 95% = 1.58-3.69; p <0.001), specifically luminal A subtype (OR = 3.59; CI 95% = 2.15 - 5.97; p <0.001). Conclusion These results indicate that the PDCD1 rs11568821 G>A polymorphism may contribute as a potential susceptibility and prognosis marker for breast cancer, especially for ER+/PR+ subtypes, considering the importance of PD-1 inhibitor effect over anti-tumor response.