Author

Yi JinFollow

Date of Award

January 2020

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Yong Zhu

Abstract

Objectives: the objective was to explore the consistency of DNA methylation pattern between peripheral blood and breast tumor tissue, and discussed the potential of using blood as a surrogate epigenetic biomarker to study the relationship between breast cancer and shiftwork.

Methods: systematic review on studies analyzing the concordance or correlation of DNA methylation level between breast tumor tissue and peripheral blood was conducted. The results of eligible studies were summarized to find the specific genes that had consistent methylation pattern in both tumor tissues and blood. Then the blood samples from the well-established Danish cohort were used to perform epigenome-wide association analysis to show the genome-wide methylation pattern in the blood. Cohort studies on each gene and its relationship between breast cancer were searched to discuss whether that gene might be a precursor for breast cancer.

Results: the DNA methylation array of the Danish cohort in this study detected 5409 CpG sites that differentially methylated between day workers and night shift workers. Totally 4750 genes showed significantly differential methylation level between the two groups. Among 22 candidate genes and 3 repetitive elements from the eligible studies and public datasets, methylation patterns of the five genes, IGF2, BRCA1, GSTP1, P16 and MGMT were consistent between blood and breast tumor tissues among breast cancer patients and showed significant difference between day shift workers and night shift workers, which implicated that it could be potential biomarkers for the screening of breast cancer and as a surrogate to study the relationship between breast cancer and circadian disruption.

Conclusion: aberrant methylation status of five genes, IGF2, BRCA1, GSTP1, P16 and MGMT, might be a promising epigenetic biomarker for early detection and diagnosis of breast cancer, and it can also be a surrogate biomarker to study the relationship between breast cancer and night shift work.

Comments

This is an Open Access Thesis.

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