A Systematic Approach to Evaluate the Infectious Etiology of Breast Cancer
Abstract
Breast cancer is the most prominent cancer in women and its unfortunate impact on women s quality of life is well known. According to the International Agency for Research on Cancer, 18%-20% of all cancer types are linked to infectious agents, and the list of definite, probable, and possible carcinogenic agents is growing each year. In this study, we aim to answer the long-debated question of whether infections are contributing to breast cancer development. Though obviously of high significance and with tremendous potential for impacting both prevention and treatment of breast cancer, this topic has received less attention and funding. Fortunately, over the last few years there has been a significant amount of interest in exploring this concept. For example, my group is a member the Avon Virus & Breast Cancer Consortium, which brings together investigators from the United States, Canada, and Australia with common research interests in this area. However, only a limited amount of foundation funding was directed to support this research. Therefore, the outcome of our research will yield a great deal of new knowledge to support or refute a role for infectious agents in breast cancer. We will apply a systematic approach to evaluate the infectious causes of breast cancer. Since infectious agents can be cleared from the organism with time and/or treatment, it is not reasonable to rely solely on the presence of infectious agents in cancer tissue as proof of their association with cancer development. Rather, we propose to focus on the "footprints" left by infectious agents regardless if these are still present in the infected breast tissue. Together, our studies address the following Overarching Challenges identified by the Breast Cancer Research Program: Identify what makes the breast susceptible to cancer development; determine why some, but not all, women get breast cancer; and prevent breast cancer (primary prevention). Specific Aims: Aim 1: To reveal key molecular signatures induced by infectious agents in normal breast epithelial cells. We propose a unique and innovative approach that relies on combining advanced technologies capable of measuring thousands of individual modifications (i.e., footprints) in infected cells with computational methods to ultimately identify patterns that are consistent with transformation of a normal cell into a tumor-like state. We will focus on the following infectious agents: Chlamydia trachomatis (Ct), human papilloma virus (HPV), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), SV40, and human mammary tumor virus (HMTV), which will be used to infect human normal primary breast epithelial cells. Aim 2: To investigate the presence of infection-induced molecular signatures in breast cancer specimens. We will test for the presence of infection-induced oncogenic signatures identified in Aim 1 using normal and cancer tissue biopsies. Our interactive approach will bring together researchers from a broad array of disciplines to provide a fresh perspective to the critically important but unanswered question regarding the infectious etiology of breast cancer. Impact: We envision that the approach taken in this project will lead to comprehensive evaluation of infectious agents and breast cancer. The infection signatures generated from this study will serve as an indicator of breast cancer etiology, which can have profound implications in all aspects of breast cancer management from prevention to treatment. By connecting infectious diseases to breast cancer, we may be able to provide explanation of why some women who do not fit into currently acknowledged risk groups get cancer. For the group of women with history of infectious diseases, there will be options for enhanced screening, such as collection of nipple aspirates to test for the presence of molecular signatures indicative of infection-induced oncogenesis in exfoliated cells. Since our studies include testin
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1610060
Entities
People
- Allen Tsang
Organizations
- United States Army
- Wake Forest University