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Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of  p 16,  ESR 1,  RASSF 1A,  RARβ 2,  CDH 13,  HIN 1,  SFRP 1 genes and the  LINE 1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes ( RASSF 1A,  RARβ 2,  CDH 13,  HIN 1 and  SFRP 1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the  CDH 13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious  CDH 13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between  CDH 13,  SFRP 1, and  RASSF 1A methylation and breast cancer subtypes and between  SFRP 1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced  RASSF 1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci ( RASSF 1A,  RAR β2 and  CDH 13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients.

Relationship between Tumor DNA Methylation Status and Patient Characteristics in African-American and European-American Women with Breast Cancer