Interethnic DNA Methylation Difference and Its Implications in Pharmacoepigenetics

Abstract

Aim: 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. Materials & methods: 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. Results: 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. Conclusion: Ethnicity should be carefully accounted for in future pharmacoepigenetics research.

Keywords::

• cancer epigenetics
• DNA methylation
• epipharmacogenomics
• population differentiation

Acknowledgements

The results published here are in part based upon data generated by TCGA Research Network: http://cancergenome.nih.gov/. Part of the material is based on the PhD thesis of the first author (S-K Chu) under the supervision of the last author (H-C Yang). The authors sincerely thank four anonymous reviewers for their very constructive and insightful comments that helped in preparing our manuscript.

Financial & competing interests disclosure

This work was partially supported by the Ministry of Science and Technology of Taiwan under Grant MOST 106–2314-B-001–003-MY3. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2017-0046

Additional information

Funding

This work was partially supported by the Ministry of Science and Technology of Taiwan under Grant MOST 106–2314-B-001–003-MY3. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.