The epidemiology of Hodgkin's disease (HD) is consistent with a viral etiology. The Epstein-Barr virus (EBV) is closely related to HD on the basis of both serologic and molecular evidence, with 30- 50% of the cases' biopsies being EBV-genome positive. Several risk factors have been consistently identified which point to age of infection as an important modifier of risk in parallel with age at diagnosis. Following the paralytic polio paradigm, both very early and late EBV infections may be more severe. How these risk factor, serologic, and molecular data fit together is unknown. We propose to address this issue in a population-based case-control study conducted in the greater Boston area and the state of Connecticut, involving 600 incident cases and 600 population controls. Risk factor data will be obtained by telephone interview; blood specimens will be drawn from the cases, and tissue blocks tested for EBV- genome. These data will be evaluated for consistency with three models of HD pathogenesis: 1. The EBV is solely related to EBV- genome positive HD with EBV-genome negative disease due to non-viral causes; 2. 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; 3. The EBV plays a crucial early role in the pathogenesis of essentially all HD cases but the genome is selectively lost in some patients. Both case-case and case-control comparisons will be done. By integrating the risk factor profile in relation to EBV-genome status of a large series of cases, we should be able to distinguish between these alternative hypotheses. This will be complimented by the serologic comparisons between the two sets of case, and in concert with data from Project 2.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA069266-04
Application #
6344728
Study Section
Project Start
2000-08-18
Project End
2001-05-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
4
Fiscal Year
2000
Total Cost
$179,222
Indirect Cost
Name
Harvard University
Department
Type
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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