Department of Cancer Prevention and Control
Roswell Park Cancer Institute
Buffalo, New York
Co-Investigator: Christine B. Ambrosone, PhD, Roswell Park Cancer Institute, Buffalo, NY
Genetic variations between individuals can confer a risk upon a person for the development of breast cancer, the age of onset of a breast cancer, the response to treatment for a breast cancer and the risk of developing a reoccurrence of a breast cancer. Employing the Framingham Study containing three generation of individuals and thousands of families, Drs. Levine and Hirshfield have identified single nucleotide polymorphisms in the p73 and MRE-11 genes (which respond to DNA damage from environmental mutagens) that result in early onset breast cancers in the next generation. They have also identified a unique polymorphism in chromosome 17q21.3 encoding a fusion protein that behaves as an oncogene altering epigenetic marks and DNA damage responses. Their findings help to explain why some cancers have genomic instability and suggest that two sets of drugs (HDAC inhibitors and PARP inhibitors) could be a useful treatment of those cancers with the fusion protein expressed. They are testing these ideas in cell culture and their research focus in 2013-2014 will continue to pursue these lines of inquiry.
In this funding period the researchers have established the infrastructure for a follow-up study of women enrolled in the Women’s Circle of Health Study (WCHS) that aims to evaluate among 1,700 African American women diagnosed with incident invasive breast cancer, the impact of obesity and obesity-related comorbidities on breast cancer treatment received and breast cancer outcomes, including quality-of-life, and determine whether optimal management of these conditions impact outcomes. Post-diagnosis blood collections are scheduled to begin in late January 2014 to examine potential mechanistic pathways mediating the impact of obesity and obesity-related comorbidities on breast cancer outcomes. The researchers also advanced their work examining biomarkers associated with psychosocial factors during the survivorship period among early stage breast cancer patients. They showed that women with high circulating 25OHD levels at the time of diagnosis and 1 year post-diagnosis were ~1.5 to 2-fold less likely to report low quality-of-life, high levels of perceived stress, depression, or fatigue compared to women with deficient 25OHD levels. Moreover, when change in circulating 25OHD levels from the time of diagnosis to 1 year post was assessed, women in the highest tertile of change were ~50% less likely to report high levels of fatigue compared to women in the lowest tertile of change. They will extend these findings to examine potential interactions between circulating 25OHD levels and immune factors. Since the last progress report 10 manuscripts citing BCRF support have been published or accepted for publication, and an R01 grant for the WCHS follow-up study was submitted based on BCRF-supported findings and scored in the 11th percentile, placing it in the fundable range.
Dr. Chi-Chen Hong received her doctorate in Epidemiology from the University of Toronto in 2004, and completed postdoctoral training with Dr. Christine Ambrosone at Roswell Park Cancer Institute (RPCI). She joined the staff of RPCI in 2008 as an Assistant Member in the Department of Cancer Prevention and Control within the Division of Cancer Prevention and Population Sciences.
Most of Dr. Hong's research is focused on breast cancer etiology, survivorship, and prognosis. Specifically, her interests are on the influence of lifestyle, genetic, and immune factors related to adiposity, diet, and hormonal exposures. She has oan ongoing prospective cohort study of early stage breast cancer patients to examine issues in breast cancer survivorship, and is co-principal investigator of a study which aims to determine if breast cancer prognosis is modified by diabetes management among breast cancer patients with type II diabetes. A main research focus is in the area of thermal dysregulation among breast cancer patients, which aims to examine potential relationships between body temperature, thermal discomfort experienced by women with breast cancer, the anti-tumor response, disease prognosis, and cytokine-driven sickness symptoms. She is currently funded to examine the role of a panel of cytokines in relation to body temperature and sickness symptoms among breast cancer patients.