Abstract: Objective To explore the association of methylation levels of C19orf57, MAP9, EMR3, NEK6 and PCOLCE2 genes in peripheral blood with breast cancer (BC) in Chinese women. Methods We collected peripheral blood samples from 258 early-stage BC patients and 272 healthy women. Agena matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was utilized to quantitatively measure the methylation levels of CpG sites in the genes. The association between DNA methylation and BC was analyzed using a logistic regression model adjusted for covariants. Spearman's correlation analysis was performed to analyze the association between the gene methylation levels and age. The methylation levels of the genes in the BC patients with different clinical characteristics were investigated using non-parametric tests. Results In stead of EMR3 gene hypermethylation as found in BC patients as found in the Caucasian population, EMR3 gene hypomethylation was found to correlate with BC in Chinese women, but this correlation was significant only in women beyond the age of 50 years (for every 10% reduction of the methylation level, EMR3_CpG_1: OR=1.40; EMR3_CpG_2: OR=2.31; EMR3_CpG_3: OR=2.76, P<0.05). EMR3 methylation was not or was only weakly correlated with tumor stage, size, lymphatic metastasis, ER, PR, HER2, or Ki67. Our data did not show a correlation between C19orf57 methylation and BC. Conclusion Peripheral blood EMR3 gene hypomethylation is associated with BC in Chinese women, especially in those at an old age and in postmenopausal women.

Key words: peripheral blood, EMR3, DNA methylation, breast cancer, MALDI-TOF