| Abstrakt: |
CpG island methylator phenotype (CIMP) involves methylation targeted toward the promoters of multiple genes. We determined a methylation profile of tumor-related genes in serum of sporadic breast cancer (SBC). The multigene methylation was examined by methylation-specific polymerase chain reaction assay in serum of 50 SBCs and 50 paired nontumors, and CIMP+ was defined as having three genes that are concordantly methylated. The methylation frequency of ten genes in serum of 50 SBCs varied from 10% in FHIT to 74% in RASSF1A. The methylation status of RASSF1A, BRCA1, p16, CDH1, ER, RARβ2, APC, and DAPK was significantly correlated with SBC and nontumor serum ( P < 0.05). Methylation of at least one gene was found in 92% SBC; CIMP was more frequent in SBC than nontumor serum ( P < 0.001). There was a significant association between CIMP and methylation of RASSF1A, BRCA1, p16, CDH1, ER, RARβ2, APC, and DAPK ( P < 0.05); the methylation link profile of CDH1, RASSF1A, BRCA1, and RARβ2 as breast cancer marker may contribute high sensitivity (90%) and specificity (88%). ER and RARβ2 methylation was associated with elevated serum CA153 levels in 39 SBC samples with CIMP+ ( P < 0.05). Multivariate analysis showed that living area of patients was found to provide independent prognostic information associated with a relative risk of tumor recurrence of 5.3. Multigene-specific methylation profile in serum was association with the recurrence risk of rural SBC, and positive correlation of CIMP can serve as a promising molecular marker of SBC. [ABSTRACT FROM AUTHOR] |
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