Methylation of Immune-Related Genes in Peripheral Blood Leukocytes and Breast Cancer.

Abnormal DNA methylation contributes to breast cancer (BC). Immune-related genes play crucial roles in BC development and progression. This study aims to investigate the effect of methylation of immune-related genes in peripheral blood leukocytes (PBLs) on BC risk. GSE51032 and GSE104942 datasets were used to identify significantly differentially methylated CpG sites (DMCs) of immune-related genes. A case-control study was conducted using MethylTarget sequencing to validate the relationship between the methylation levels of the screened genes and BC risk. We also evaluated the association between methylation haplotypes of screened genes and BC risk. Moreover, we sorted the blood leukocytes into T cells, B cells, and monocytes to detect the difference of DNA methylation in different cell subtypes. A total of five DMCs were screened from GEO datasets, including cg01760846 (), cg07141527 (), cg15658543 (), cg21568368 (), and cg24045276 (). In the case-control study, there were significant associations between methylation of the CpG sites in the five genes and BC risk. Methylation haplotype burdens of , , and were associated with reduced BC risk. Moreover, there were heterogeneities in the methylation levels of the genes in different cell subtypes. In conclusion, methylation of , , , , and in PBLs were associated with BC risk. The five-gene methylation could be the potential biomarkers for predicting BC risk.