Thomas E. Rohan, MD, PhD

2009-2010 BCRF Project:
Intervention prior to the development of breast cancer represents one means by which the burden of this disease can be reduced. In this regard, women with benign breast disease are of particular interest given the considerable morbidity and the increased breast cancer risk associated with this condition. The goal of Dr. Rohan's project is to develop methods to examine the expression levels of many genes examined simultaneously (gene expression profiling) and similarly for proteins (proteomic profiling). He postulates that these approaches might be useful in predicting the risk of progression of benign breast disease to subsequent breast cancer and hence that they might be of use for the clinical management of such women.

For the gene expression component of their work, Dr. Rohan and colleagues have now completed the RNA extraction and preparation from the benign breast tissue samples, and at the time of last report expected to have completed assay processing by late June. They will then proceed to data analysis. For the proteomic component of our work, they have identified the optimal conditions for the Barofold (pressure) method and are now in the process of analyzing samples in triplicate. Additionally, they have commenced work on the other two methods that they will evaluate (sonication, and the Expression Pathology method). Having identified the optimal proteomic method, they will apply this to tissue samples from their benign breast disease cohort.

For the coming year, Dr. Rohan and colleagues propose two projects. The first extends their work on gene expression profiling of benign breast tissue to encompass epigenetic profiling. Aberrant DNA methylation is considered to occur early in cancer development. Their goal is to develop methods to test the hypothesis that the methylation profile of benign breast tissue can identify women at risk of progressing to breast cancer, for ultimate application in an epidemiologically well-characterized cohort that consists of 15,395 women who had a biopsy for benign breast disease, for whom formalin-fixed paraffin-embedded (FFPE) benign breast tissue is available, and who have been followed up to determine the subsequent occurrence of breast cancer. To date, there are almost 600 cases of breast cancer in the cohort. The ultimate goal of this work is to enhance approaches to the prediction of breast cancer risk and to the clinical management of women at risk.

The second project represents a new direction: the role of oxidative stress in the etiology of breast cancer. Oxidative stress is a disturbance in the balance between the production of reactive species (RS)(unstable molecules that react with and damage DNA) and antioxidant defences, resulting in a relative excess of RS. Oxidative stress is considered to have a role in carcinogenesis. Furthermore, oxidative stress might be associated with breast cancer risk. However, this hypothesis has received relatively little epidemiologic scrutiny. Therefore, Dr. Rohan proposes to study the association between an oxidative stress score (based on exposures to pro- and anti-oxidants) and breast cancer risk in the Canadian Study of Diet, Lifestyle, and Health, a cohort study that includes 39,618 women who completed dietary and lifestyle questionnaires on recruitment (and also provided biological specimens). The work will entail completing record linkages to cancer registries to identify breast cancer cases in the cohort (n=1015 expected), coding and entering questionnaire data, obtaining information on estrogen/progesterone receptor status, and conducting the statistical analysis. The proposed study should provide further insight into the role of oxidative stress in the etiology of breast cancer, and lay the groundwork for subsequent etiologic studies.

Bio:
Dr. Rohan received his MD (awarded as M.B., B.S.) from the University of Adelaide in Australia in 1975. Subsequently, he obtained an MSc. in Epidemiology at the London School of Hygiene and Tropical Medicine before returning to Adelaide, where he obtained his PhD in Epidemiology in 1986. After stints at St. Bartholomew's Hospital and with the Medical Research Council in London, England, and at the University of Toronto in Toronto, Canada, he moved to New York in 2000 to take up his current positions.

Dr. Rohan is a cancer epidemiologist whose research focuses largely on the etiology and pathogenesis of breast cancer. He has conducted numerous investigations into the roles of molecular, nutritional, and hormonal factors in the etiology of benign breast disease and of breast cancer. He has served on a many site visit and peer review panels, and recently completed a term as a permanent member of the NIH Epidemiology of Cancer Study Section. Dr. Rohan reviews regularly for many journals, and is an Associate Editor of Cancer Epidemiology, Biomarkers, and Prevention. He has published more than 200 articles and book chapters, and has edited 2 books.