Human T-Lymphoma Virus Type I Clinical Trial
Official title:
Prediagnostic Markers of Adult T-Cell Leukemia/Lymphoma Among Carriers of Human T-Lymphoma Virus Type I: A Collaborative Study
This study will identify chemical and protein markers in the blood of people who carry the
human T-lymphotropic virus type I (HTLV-I), a virus associated with various pathologies,
including an increased risk in adults of a rare and aggressive cancer called adult T cell
leukemia/lymphoma (ATL). The study will also examine differences in these markers before and
after the onset of ATL.
ATL has been reported in every area where HTLV-1 is common, including the Caribbean and parts
of Japan, West Africa, the Middle East, South America, and Pacific Melanesia. Risk factors
for the disease are largely unknown and seem to vary among those affected in different
endemic regions. People who acquire the infection early in life are thought to be at higher
risk than those who are infected later. In Japan, men seem to be at greater risk than women,
but the same is not evident among the black population in the Caribbean and Brazil.
Findings from this study will increase understanding of the cause of ATL and identify
differences in tumor characteristics and the course of disease across geographical areas.
Study subjects are drawn from among participants in eight studies of HTLV-1 carriers,
including the 1) Jamaica Mother-Infant Cohort Study, 2) Jamaica Family Study, 3) Jamaica Food
Handlers Study, 4) Miyazaki Cohort Study in Japan, 5) Nagasaki Cohort Study in Japan, 6)
Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Disease, 7)
HTLV Outcome Studies in the United States, and 8) GIPH Cohort Study in Brazil.
Stored blood samples previously collected from patients in the above studies who did and did
not develop ATL will be analyzed for immunologic and genetic factors.
To characterize molecular markers for risk of adult T-cell leukemia/lymphoma (ATL), whose
incidence rate differs greatly across geographic areas, we propose to examine the prevalence
and level of viral and host immune response markers as well as the protein expression pattern
of 57 subjects who subsequently developed ATL and 171 matched control subjects who
participated in various prospective studies of carriers of human T-lymphotropic virus type I
(HTLV-I). Informative markers to be studied include provirus load, HTLV-I antibody titer,
anti-Tax protein, clonality of HTLV-I infected lymphocytes (viral markers), total
immunoglobulin E (IgE), C-reactive protein (CRP), neopterin, soluble CD30, soluble
interleukin-2 receptor (sIL2-R), EBV antibody profile (host immune markers), and proteomics.
These markers were selected based on the measurability on the majority of specimens,
availability of validated assays, relevance to the biology of T-cell malignancies, and has
been used in a cross-sectional comparison of HTLV-I carriers and non-carriers from Japan and
the Caribbean. We will utilize central laboratory and validated, standard assays for all
specimens. The results, unlinked to personal identifiers, will be analyzed using generalized
estimating equation. The findings will further our understanding of the etiology of ATL, and
of differences in natural history of HTLV-I infection across geographic areas.
While pursuing the same theme of trying to identify host and viral markers associated with
ATL, the unique aspect of this proposal is to pool ATL cases, an extremely rare malignancy,
from multiple epidemiologic studies through international collaboration, in order to achieve
adequate statistical power and to perform valid comparison of tumor characteristics across
geographic areas.
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