Date of Award

January 2014

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Yong Zhu

Abstract

As the leading source of cancer death among women worldwide, breast cancer has experienced a steady increase in prevalence in recently years, a trend that is most evident in industrialized nations. One possible explanation for this epidemic phenomenon is the exposure to light at night through shiftwork, which has been linked to both aberrant DNA methylation and increased risk of breast cancer development. Based on a whole-genome methylation analysis on a selected sample of the Danish Diet, Cancer and Health prospective cohort, we observed statistically significant hypomethylation in the PIWIL1 gene, a member of the PIWI protein family, among night shiftworkers. Upon analysis of expression microarray data from the Oncomine database, we observed a trend of PIWI gene overexpression in breast cancer patients relative to healthy controls. This finding was confirmed when we measured the endogenous expression of PIWI genes in breast cell lines, which revealed overexpression of PIWIL1 and PIWIL4 in breast cancer cells relative to normal breast cells. To further elucidate the functional link between PIWI gene expression and breast cancer, we knocked down PIWIL1 and L4 in breast cancer cells and observed a substantial decrease in the rate of cellular proliferation, which suggests that these genes may play a role in the breast carcinogenic process. Future in-depth investigation into the function of PIWI genes is warranted to gain a more comprehensive understand of their role in breast carcinogenesis.

Comments

This is an Open Access Thesis.

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