Study of Adult T-Cell Leukemia/Lymphoma Among Carriers of HTLV-1
| Status: | Completed |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/21/2016 |
| Start Date: | December 2004 |
| End Date: | May 2011 |
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.
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.
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.
- INCLUSION CRITERIA:
CASES:
Incident ATL cases will be identified from the various study cohorts. For Jamaica Family
Study, in which prevalent cases were enrolled, we will only include cases that occurred
among initially unaffected family members. The diagnosis of ATL follows universal criteria
for all cohorts. For each case, one prediagnostic specimen will be analyzed. If there are
more than one prediagnostic specimens, we will select the earliest drawdate from which
both serum/plasma and DNA specimens are available. Whenever available, one postdiagnostic
specimen will also be considered for analysis of longitudinal changes in marker levels.
CONTROLS:
Fro each index case, 2 age-, sex-, screen-matched asymptomatic HTLV-I carriers will be
selected as controls, from within the same cohort in which the case arose (risk set
sampling). For Jamaica Family Study, the control subjects are selected from unrelated
subjects (such as spouses or incidental recruit unrelated to the index case) or from one
or two population-based studies of unrelated subjects (i.e., food handlers study or
mother-infant cohort study). For controls, specimens collected close to the time of pre-
and post-diagnostic phlebotomy for the case will be analyzed.
We found this trial at
3
sites
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials