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

PDCD1基因单核苷酸多态性和单倍型与乳腺癌发生风险增加相关。

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Abstract

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 (BC) patients and cancer-free women and correlate them with clinical-pathological parameters. 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. The fragments were separated by acrylamide gel electrophoresis for genotyping. 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 BC (OR = 2.42; CI 95% = 1.59-3.69; P < 0.001). This polymorphism was also correlated with positivity for estrogen (τ = 0.25; P < 0.001) and progesterone receptors (τ = 0.17; P = 0.021). The haplotypic analysis also indicated that AC allele carriers have a higher risk of BC 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). These results indicate that the PDCD1 rs11568821 G > A polymorphism may contribute as a potential susceptibility and prognosis marker for BC, especially for ER+/PR+ subtypes, considering the importance of PD-1 inhibitor effect over antitumor response.

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