Dr. Chow's long-term goal is to become an independent, patient-oriented investigator focused on understanding the metabolic and cardiovascular (CV) complications affecting cancer survivors. A rigorous didactic and mentoring program in outcomes research and genetic epidemiology will provide the applicant the foundation to comprehensively examine treatment, environmental, and host factors that influence CV disease following cancer treatment. Specifically, he proposes to investigate determinants of adverse CV late effects following hematopoietic cell transplantation (HCT). Refinements in HCT have led to an increasing number of long-term survivors and a need to better characterize causes of morbidity and mortality in this population besides relapse and chronic graft versus host disease (GVHD). Survivors appear to be at increased risk of adverse late effects such as hypertension, dyslipidemia, and diabetes, all of which contribute to increased CV morbidity and mortality. Purported risk factors include: 1) pre-transplant anthracycline and radiotherapy exposure, which are associated with late cardiomyopathy, valvular and vascular injury;and 2) chronic GVHD and total body irradiation (TBI), which are hypothesized to cause endothelial injury and atherosclerosis. Previous studies have been limited by selection and recall biases, small sample size, and evaluation of primarily clinical factors without consideration of genetic determinants. Data from centralized registries contain larger samples, but often lack detailed pre-HCT treatment, environmental exposure, and genetic information. To address these limitations, Dr. Chow proposes to study a cohort of nearly 5000 e2 yr HCT survivors treated at the Fred Hutchinson Cancer Research Center (FHCRC) since 1969. This cohort has advantages of an exceptional clinical research database at FHCRC with <1% loss to follow-up, and availability of hospital discharge and death records, and patient questionnaires documenting medical, environmental, and family histories relevant to CV disease. This cohort, with improved phenotypic characterization of CV outcomes supplemented by enriched environmental and family histories, will facilitate more in-depth analyses (via a nested case-cohort design) of risk factors that predispose towards CV disease in this population, including meaningful investigation of genetic variation. Existing genome-wide variation data collected at FHCRC will be used to identify novel loci and to replicate prior published associations. Overall, these results will allow better classification of individuals who may be at increased risk of late CV disease and give clinicians and patients an opportunity to modify therapy and/or develop more targeted post-HCT surveillance with earlier intervention. This research also has direct relevance to the larger population of cancer survivors who receive similar treatment exposures. Completion of these aims will provide the candidate with the necessary skills, experience, and preliminary data to launch an independent research program.

Public Health Relevance

Dr. Chow's long-term goal is to become an independent clinical investigator focused on understanding the metabolic and cardiovascular complications affecting cancer survivors. To accomplish this, he proposes to comprehensively study risk factors associated with subsequent cardiovascular disease in survivors of hematopoietic cell transplantation, by examining the influence of genetics with treatment and lifestyle exposures.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA151775-04
Application #
8699021
Study Section
Subcommittee B - Comprehensiveness (NCI)
Program Officer
Perkins, Susan N
Project Start
2011-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109
Leger, Kasey J; Baker, K Scott; Cushing-Haugen, Kara L et al. (2018) Lifestyle factors and subsequent ischemic heart disease risk after hematopoietic cell transplantation. Cancer 124:1507-1515
Chow, Eric J; Antal, Zoltan; Constine, Louis S et al. (2018) New Agents, Emerging Late Effects, and the Development of Precision Survivorship. J Clin Oncol 36:2231-2240
Chow, Eric J; Chen, Yan; Hudson, Melissa M et al. (2018) Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer. J Clin Oncol 36:44-52
Armenian, Saro H; Yang, Dongyun; Teh, Jennifer Berano et al. (2018) Prediction of cardiovascular disease among hematopoietic cell transplantation survivors. Blood Adv 2:1756-1764
Armenian, Saro H; Chemaitilly, Wassim; Chen, Marcus et al. (2017) National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Cardiovascular Disease and Associated Risk Factors Working Group Report. Biol Blood Marrow Transplant 23:201-210
Chow, Eric J; Cushing-Haugen, Kara L; Cheng, Guang-Shing et al. (2017) Morbidity and Mortality Differences Between Hematopoietic Cell Transplantation Survivors and Other Cancer Survivors. J Clin Oncol 35:306-313
Leger, Kasey J; Cushing-Haugen, Kara; Hansen, John A et al. (2016) Clinical and Genetic Determinants of Cardiomyopathy Risk among Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant 22:1094-1101
Chow, Eric J; Anderson, Lynnette; Baker, K Scott et al. (2016) Late Effects Surveillance Recommendations among Survivors of Childhood Hematopoietic Cell Transplantation: A Children's Oncology Group Report. Biol Blood Marrow Transplant 22:782-95
Chow, Eric J; Stratton, Kayla L; Leisenring, Wendy M et al. (2016) Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 17:567-76
Chow, Eric J; Asselin, Barbara L; Schwartz, Cindy L et al. (2015) Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group. J Clin Oncol 33:2639-45

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