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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Academic/Teacher Award (ATA) (K07)
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Study Section
Subcommittee B - Comprehensiveness (NCI)
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Perkins, Susan N
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Fred Hutchinson Cancer Research Center
United States
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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
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 22:1094-101
Feijen, Elizabeth A M; Leisenring, Wendy M; Stratton, Kayla L et al. (2015) Equivalence Ratio for Daunorubicin to Doxorubicin in Relation to Late Heart Failure in Survivors of Childhood Cancer. J Clin Oncol 33:3774-80
Chow, Eric J; Chen, Yan; Kremer, Leontien C et al. (2015) Individual prediction of heart failure among childhood cancer survivors. J Clin Oncol 33:394-402
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
Armenian, Saro H; Chow, Eric J (2014) Cardiovascular disease in survivors of hematopoietic cell transplantation. Cancer 120:469-79
Chow, Eric J; Wong, Kenneth; Lee, Stephanie J et al. (2014) Late cardiovascular complications after hematopoietic cell transplantation. Biol Blood Marrow Transplant 20:794-800
Chow, Eric J; Baker, K Scott; Lee, Stephanie J et al. (2014) Influence of conventional cardiovascular risk factors and lifestyle characteristics on cardiovascular disease after hematopoietic cell transplantation. J Clin Oncol 32:191-8
Lipshultz, Steven E; Diamond, Melissa B; Franco, Vivian I et al. (2014) Managing chemotherapy-related cardiotoxicity in survivors of childhood cancers. Paediatr Drugs 16:373-89

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