<i>CCDC12</i> gene methylation in peripheral blood as a potential biomarker for breast cancer detection

Aberrant DNA methylation has been identified as biomarkers for breast cancer detection. Coiled-coil domain containing 12 gene (<i>CCDC12</i>) implicated in tumorigenesis. This study aims to investigate the potential of blood-based <i>CCDC12</i> methylation for breast cancer detection. DNA methylation level of CpG sites (Cytosine-phosphate Guanine dinucleotides) in <i>CCDC12</i> gene was measured by mass spectrometry in 255 breast cancer patients, 155 patients with benign breast nodules and 302 healthy controls. The association between <i>CCDC12</i> methylation and breast cancer risk was evaluated by logistic regression and receiver operating characteristic curve analysis. A total of eleven CpG sites were analyzed. The <i>CCDC12</i> methylation levels were higher in breast cancer patients. Compared to the lowest tertile of methylation level in CpG_6,7, CpG_10 and CpG_11, the highest quartile was associated with 82, 91 and 95% increased breast cancer risk, respectively. The <i>CCDC12</i> methylation levels were associated with estrogen receptor (ER) and human epidermal growth factor 2 (HER2) status. In ER-negative and HER2-positive (ER-/HER2+) breast cancer subtype, the combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER−/HER2+ breast cancer from the controls (AUC = 0.727). The hypermethylation levels of <i>CCDC12</i> in peripheral blood could be used for breast cancer detection. Breast cancer detection could be facilitated by novel blood-based DNA methylation biomarkers.The methylation levels of CpG sites in <i>CCDC12</i> were higher in breast cancer than those in controls.The combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER-/HER2+ breast cancer subtype from the controls. Breast cancer detection could be facilitated by novel blood-based DNA methylation biomarkers. The methylation levels of CpG sites in <i>CCDC12</i> were higher in breast cancer than those in controls. The combination of four sites CpG_2, CpG_5, CpG_6,7 and CpG_11 methylation levels could distinguish ER-/HER2+ breast cancer subtype from the controls.