DNA Methylation of Imprinted Genes KCNQ1, KCNQ1OT1, and PHLDA2 in Peripheral Blood Is Associated with the Risk of Breast Cancer

DNA甲基化 甲基化 CpG站点 基因组印记 乳腺癌 印记(心理学) 外周血 表观遗传学 癌症 生物 医学 肿瘤科 遗传学 基因 内科学 基因表达
作者
Jinming Fu,Lei Zhang,Dapeng Li,Tian Tian,Xuan Wang,Hongru Sun,Anqi Ge,Yupeng Liu,Xianyu Zhang,Hao Huang,Shuhan Meng,Ding Zhang,Liyuan Zhao,Simin Sun,Ting Zheng,Chenyang Jia,Yashuang Zhao,Da Pang
出处
期刊:Cancers [Multidisciplinary Digital Publishing Institute]
卷期号:14 (11): 2652-2652 被引量:9
标识
DOI:10.3390/cancers14112652
摘要

Methylation alterations of imprinted genes lead to loss of imprinting (LOI). Although studies have explored the mechanism of LOI in breast cancer (BC) development, the association between imprinted gene methylation in peripheral blood and BC risk is largely unknown. We utilized HumanMethylation450 data from TCGA and GEO (n = 1461) to identify the CpG sites of imprinted genes associated with BC risk. Furthermore, we conducted an independent case-control study (n = 1048) to validate DNA methylation of these CpG sites in peripheral blood and BC susceptibility. cg26709929, cg08446215, cg25306939, and cg16057921, which are located at KCNQ1, KCNQ1OT1, and PHLDA2, were discovered to be associated with BC risk. Subsequently, the association between cg26709929, cg26057921, and cg25306939 methylation and BC risk was validated in our inhouse dataset. All 22 CpG sites in the KCNQ1OT1 region were associated with BC risk. Individuals with a hypermethylated KCNQ1OT1 region (>0.474) had a lower BC risk (OR: 0.553, 95% CI: 0.397−0.769). Additionally, the methylation of the KCNQ1OT1 region was not significantly different among B cells, monocytes, and T cells, which was also observed at CpG sites in PHLDA2. In summary, the methylation of KCNQ1, KCNQ1OT1, and PHLDA2 was associated with BC risk, and KCNQ1OT1 methylation could be a potential biomarker for BC risk assessment.
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