Recent findings on Hodgkin's disease (HD) present a number of important questions. The established risk factors point to age of infection as an important modifier of risk. Cases have altered antibody profiles to the Epstein-Barr virus (EBV) preceding and following diagnosis. The new finding is that 30-50% of HD cases' tumors contain monoclonal EBV genome, with a restricted latent protein expression. How these risk factor, serologic, and molecular data fit together and whether EBV-genome negative HD represents a separate etiology are unknown. This Program Project is designed to test three alternate models of the role of the EBV in the pathogenesis of HD: the EBV is solely related to EBV-genome positive HD with EBV-genome negative disease due to non-viral causes; HD is a virally induced malignancy with the EBV responsible for EBV-genome positive disease and another unidentified virus(es) linked to EBV- genome negative disease; or the EBV plays a crucial early role in the pathogenesis of essentially all HD cases but the genome is selectively lost in some patients. Three companion projects will address the following: the role of EBV in the epidemiology of HD (600 cases and 600 population controls); the association of pre- diagnosis EBV serology with EBV genome status of tumor biopsy in HD (200 cases and 200 matched controls); and characterization of the EBV infection and the cellular immune response in HD cases (160 cases and 160 bone marrow donor controls). The Projects are supported by a serology/pathology Core and an Administrative Core. The combined mutually standardized data from the population studies, plus extensive biomarkers including EBV serology and viral probes, and detailed immunologic markers will result in a substantial and rich database. The program brings together an experienced multi- disciplinary group of investigators; by working together we should gain insight into the etiology of HD.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA069266-03
Application #
2895439
Study Section
Subcommittee G - Education (NCI)
Program Officer
Patel, Appasaheb1 R
Project Start
1997-06-20
Project End
2002-05-31
Budget Start
1999-09-24
Budget End
2000-05-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Levin, Lynn I; Breen, Elizabeth C; Birmann, Brenda M et al. (2017) Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis. Cancer Epidemiol Biomarkers Prev 26:1114-1123
Epstein, Mara M; Chang, Ellen T; Zhang, Yawei et al. (2015) Dietary pattern and risk of hodgkin lymphoma in a population-based case-control study. Am J Epidemiol 182:405-16
Li, Qian; Chang, Ellen T; Bassig, Bryan A et al. (2013) Body size and risk of Hodgkin's lymphoma by age and gender: a population-based case-control study in Connecticut and Massachusetts. Cancer Causes Control 24:287-95
Gao, Yongshun; Li, Qian; Bassig, Bryan A et al. (2013) Subtype of dietary fat in relation to risk of Hodgkin lymphoma: a population-based case-control study in Connecticut and Massachusetts. Cancer Causes Control 24:485-94
Levin, Lynn I; Chang, Ellen T; Ambinder, Richard F et al. (2012) Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma. Blood 120:3750-5
Kasperzyk, Julie L; Chang, Ellen T; Birmann, Brenda M et al. (2011) Nutrients and genetic variation involved in one-carbon metabolism and Hodgkin lymphoma risk: a population-based case-control study. Am J Epidemiol 174:816-27
Chang, Ellen T; Birmann, Brenda M; Kasperzyk, Julie L et al. (2009) Polymorphic variation in NFKB1 and other aspirin-related genes and risk of Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 18:976-86
Fu, De-Xue; Tanhehco, Yvette; Chen, Jianmeng et al. (2008) Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors. Nat Med 14:1118-22
Chang, Ellen T; Zheng, Tongzhang; Weir, Edward G et al. (2004) Aspirin and the risk of Hodgkin's lymphoma in a population-based case-control study. J Natl Cancer Inst 96:305-15
Chang, Ellen T; Zheng, Tongzhang; Lennette, Evelyne T et al. (2004) Heterogeneity of risk factors and antibody profiles in epstein-barr virus genome-positive and -negative hodgkin lymphoma. J Infect Dis 189:2271-81

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