Epigenetic markers-based breast cancer early detection method development

Abstract

Relevance: According to the International Agency for Research on Cancer (IARС), breast cancer ranks
 1st-2nd among other cancers globally [1], including
 Kazakhstan [2]. In Kazakhstan, the annual growth
 in breast cancer incidence exceeds 26.6%. In 2018-
 2019, breast cancer was the 3rd most common cause
 of cancer death in Kazakhstan, accounting for 8.7-8.1
 per cent, respectively. Early detection of breast cancer
 remains an acute issue. In particular, early detection
 should be improved. Epigenetic studies of cancer patients confirm that epigenetic biomarkers could be
 used as early cancer diagnostic markers, including
 breast cancer.
 The purpose was to find specific diagnostic markers by methylation profiling of peripheral blood mononuclear fraction DNA in breast cancer patients.
 Results: Plasma samples of the Kazakhstani population with breast cancer possessed mononuclear
 fraction methylation markers in CpG islets associated
 with JAM3, C17orf64, MSC, and C7orf51 genes and the
 CpG islet associated with the intragenic region of the 5,
 chr5: 77,208,034-77,329,434 chromosome, which were
 missing in healthy individuals. These biomarkers allow
 differentiating breast cancer from other cancers with a
 specificity of 0.91 and a sensitivity of 0.94 compared to
 methylation data from open DNA methylation databases (for Illumina 450K): TCGA, GSE40279, GSE61496,
 GSE76269 и GSE66836.
 Conclusion: Early breast cancer detection method using peripheral blood mononuclear fraction DNA
 methylation profile, namely in CpG islets associated
 with JAM3, C17orf64, MSC, and C7orf51 genes and the
 CpG islet associated with the intragenic region of the
 5, chr5: 77,208,034-77,329,434 chromosome is enough
 specific and sensitive to use it in breast cancer screening