Interethnic DNA methylation difference and its implications in pharmacoepigenetics.

Abstract

This is the first systematic study to examine the population differentiation effect of DNA methylation on the treatment response and drug absorption, distribution, metabolism and excretion in multiple tissue types and cancer types. We analyzed the whole methylome and transcriptome data of primary tumor tissues of four cancer types (breast, colon, head & neck and uterine corpus) and lymphoblastoid cell lines for African and European ancestry populations. Ethnicity-associated CpG sites exhibited similar methylation patterns in the two studied populations, but the patterns differed between tumor tissues and lymphoblastoid cell lines. Ethnicity-associated CpG sites may have triggered gene expression, influenced drug absorption, distribution, metabolism and excretion, and showed tumor-specific patterns of methylation and gene regulation. Ethnicity should be carefully accounted for in future pharmacoepigenetics research.