Wednesday, December 4, 2024
12/4/2024
PROJECT SUMMARY With the rapidly aging population and improved survival rate, the number of breast cancer survivors in the U.S. is projected to reach 4.4 million by 2030, among which more than 60% of them will be aged ≥65 years. A key issue facing older cancer survivors is the impact of cancer and its treatment on their cognition. Cancer and brain aging have both common and distinct etiologies. For example, shared germline genetic heritability was identified between breast cancer and Alzheimer’s disease (AD) in large cross-trait genetic analyses, while other studies showed differential regulation of p53 and Pin1 in cancer and AD. Compelling clinical and observational studies report deficits in cognitive functioning in women diagnosed and treated for breast cancer over the short-term (<2 years), and consistently support acute toxicity of chemotherapies on cognition (i.e., chemo-brain). In contrast, population studies, often with long follow-up (>10 years), show lower incidence of AD in cancer survivors compared with cancer-free controls. While these inverse associations have persisted in studies with attempts to reduce diagnostic and competing risk biases, the possibility of survival bias, which would increase with time since cancer diagnosis, cannot be ruled out. Until we can determine how breast cancer and its treatment (chemotherapy, radiation, and hormone therapy) affect cognitive trajectory, we will not be able to improve quality of life and care for breast cancer survivors. However, most previous research is limited by a lack of (a) consideration of both the short- and long-term effect of breast cancer on cognition (which may reduce survival bias for breast cancer with a 5-year relative survival rate of 90%); (b) repeated global and domain specific cognition measures before and after treatment; (c) focus on the role of post-diagnostic lifestyles in the treatment- cognition relation; (d) investigation of gene-treatment interactions; (e) and identification of shared and distinct molecular etiologies of cancer and AD. The overarching goal of this proposal is to comprehensively determine the association of breast cancer diagnosis and treatment with cognitive trajectory over time, and identify the intersection of cancer hallmark pathways with AD to inform targeted intervention. This proposal leverages the unique resources from the Nurses’ Health Study with follow-up of 3,120 breast cancer survivors for >30 years, and repeatedly collected objective cognitive assessments; and the Gene Expression Omnibus with 2,520 human brain transcriptomics on AD patients and controls, and addresses the following hypothesis: (1) Women diagnosed and treated with cancer experience more rapid cognitive decline over the short-term, and (2) Cancer hallmarks of genomic instability, oxidative stress and inflammation are shared mechanisms between cancer and AD, but the hallmarks of proliferation and cellular pluripotency are differentially regulated. Dr. Peng plans to receive training in areas of aging research, cancer survivorship, advanced statistical modeling, and professional skill development. Together, the scientific and training components of this K01 will position Dr. Peng to become an independent interdisciplinary investigator specialized in the integration of aging and cancer research.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
