This study will explore the epidemiology of subtypes of Hodgkin's disease (HD) defined by Epstein-Barr virus (EBV). Recent identification of EBV in HD tumors has implicated this common virus as a causal cofactor to half the cases. While laboratory studies report intriguing differences between EBV-positive and -negative HD cases, these data are sparse, and they lack technical uniformity and epidemiologic focus. Thus, epidemiologic risk factors, including HIV and the incidence rate of EBV-defined HD, remain poorly defined, although EBV classification of HD tumors has significance for the etiology, surveillance, and prevention of HD through vaccination. The investigators state that this study will be the first to characterize EBV-defined HD in a population-based case series uniformly tested with reliable EBV assays, pathologically re-reviewed, and large enough for the detailed examination required by the complex epidemiology of HD. This study aims to: 1) collect archived tumor specimens from 1990-1995 incident HD cases reported to the population-based California Cancer Registry (CCR); 2) apply standard molecular techniques to test for EBV latent gene products so as to classify each case as EBV-positive or -negative; 3) calculate risks of EBV-positive and -negative HD for variables suggested to characterize EBV-defined HD and available in the CCR database (age, sex, race, birth place, disease site and stage) or determined by this study (re-reviewed histologic subtype, linkage-based AIDS status); 4) calculate incidence rates for EBV-positive and -negative HD, and standardized incidence ratios to determine if AIDS is associated with HD; 5) bank tumor specimens for future testing. The investigators will acquire case listings from several large CCR regions, select a stratified random sample, and request tumor specimens for 2,543 subjects. They will test the 2,140 they expect to obtain for EBV gene products using EBER in situ hybridization with positive and negative controls; and conduct EBV stain-typing and LMP-1 sequencing to further explore EBV positivity. They will link the database to study-area population-based AIDS registries to determine AIDS status. Data analysis will compare EBV-positive and -negative HD by study variables using descriptive statistics; multivariate analyses to test hypotheses about EBV risks among subgroups; and calculation of incidence rates and standardized incidence ratios. The investigators point out that study strengths include timely exploration of HD risks associated with a common virus (EBV) with prevention potential; a population-based case series large enough for relevant, detailed analysis; uniform application of state-of-the-art molecular assays; use of existing cancer and AIDS databases augmented by molecular data; expert pathology re-review; and the first examination of AIDS-linked HD and EBV in population-based, re-reviewed cases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA065661-02
Application #
2733116
Study Section
Special Emphasis Panel (ZRG4-EDC-1 (04))
Program Officer
Patel, Appasaheb1 R
Project Start
1997-09-22
Project End
2000-06-30
Budget Start
1998-07-17
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northern California Cancer Center
Department
Type
DUNS #
City
Fremont
State
CA
Country
United States
Zip Code
94538
Glaser, S L; Clarke, C A; Chang, E T et al. (2014) Hodgkin lymphoma incidence in California Hispanics: influence of nativity and tumor Epstein-Barr virus. Cancer Causes Control 25:709-25
Glaser, Sally L; Gulley, Margaret L; Clarke, Christina A et al. (2008) Racial/ethnic variation in EBV-positive classical Hodgkin lymphoma in California populations. Int J Cancer 123:1499-507
Glaser, Sally L; Clarke, Christina A; Gulley, Margaret L et al. (2003) Population-based patterns of human immunodeficiency virus-related Hodgkin lymphoma in the Greater San Francisco Bay Area, 1988-1998. Cancer 98:300-9