The Associations between Immunity-Related Genes and Breast Cancer Prognosis in Korean Women

<div><p>We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS) in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS) were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs) in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA). A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell’s C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP) was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at <i>p</i>-value less than 0.05. The most significant SNPs were rs1952438 in <i>SOCS4</i> gene (hazard ratio (HR) = 11.99, 95% CI = 3.62–39.72, <i>P</i> = 4.84E-05), rs2289278 in <i>TSLP</i> gene (HR = 4.25, 95% CI = 2.10–8.62, <i>P</i> = 5.99E-05) and rs2074724 in <i>HGF</i> gene (HR = 4.63, 95% CI = 2.18–9.87, <i>P</i> = 7.04E-05). In the polygenic risk score model, the HR of women in the 3^rd tertile was 6.78 (95% CI = 1.48–31.06) compared to patients in the 1^st tertile of polygenic risk score. Harrell’s C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (<i>P</i><0.1<i>)</i>. The <i>IL-6R</i>, <i>IL-8</i>, <i>IL-10RB</i>, <i>IL</i>-<i>12A</i>, and <i>IL</i>-<i>12B</i> was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women.</p>