Association between programmed death protein 1-related single-nucleotide polymorphisms and immune-related adverse...

Programmed death protein 1 (PD-1) inhibitors have potent anti-tumor activities. However, they often result in immune-related adverse events (irAEs) of varying severity. Therefore, the factors affecting the incidence of irAEs warrant urgent investigation. This study aimed to identify specific and sensitive predictors of irAEs in a Chinese population. We conducted a genome-wide association study (GWAS) comprising 80 patients with malignant tumors to evaluate single-nucleotide polymorphism (SNP) loci associated with the incidence of irAEs. The SNP rs2157775 on the LOC339166 gene had the lowest P value but did not reach the significance threshold after Bonferroni correction. Therefore, potentially associated SNPs were further investigated through the mechanism-related PD-1 pathway using the ImmPort and PathCards Human Gene Databases. A binary logistic regression model revealed that CD3E (rs3782040) A/A was associated with a lower incidence of irAEs in patients with malignant tumors who received PD-1 inhibitors. In contrast, PTPN11 (rs143894582) C/CA was associated with a higher incidence of irAEs. These findings provide a basis for the verification and identification of new loci to provide insight into the etiology of irAEs.