Molecular Genetics Study of Nasopharyngeal Carcinoma: Characterization of NPC Susceptibility Gene(s)
The objective of this study is to characterize genes associated either with susceptibility
or resistance to the development nasopharyngeal carcinoma (NPC) in a Chinese population
where the incidence of NPC is as high as 50 in 100,000. NPC has been and remains a unique
model of human malignancy for understanding a multi-step carcinogenic process involving a
ubiquitous virus (Epstein-Barr virus), environmental carcinogens, and an NPC susceptibility
gene. Up to 95% of all NPC patients at early or late stage of the disease have IgA
antibodies directed to the EBV virus VCA (viral capsid antigen). Environmental factors have
also been implicated as significant risk factors in the development of NPC. In addition,
certain alleles in HLA genes have shown associations with NPC, perhaps in concert with a
family of T-cell receptor genes (TCR). Other data suggest that a microsatellite marker on
Chromosome 6 may be associated with an NPC-disease associated gene.
We will use a "triad" approach to attempt to dissociate genetic from environmental and viral
associations of NPC incidence. Blood samples will be collected from volunteers (probands)
and family members (spouse and child and/or parent of patient) at two sites in Guangxi
Province, China: the Cancer Research and Control Institute in Wuzhou City; and the Cang Wu
County Cancer Hospital, located about 20 miles from Wuzhou. All cases will be EBV/IgA/VCA
positive. These triad of samples will provide both control and haplotypic information on
cases and controls. A database of pertinent clinical and family information will be created
from a questionnaire filled in by hospital staff interviewers. Blood will be separated into
plasma and peripheral blood mononuclear cells (PBMCs). Plasma will be tested at the Wuzhou
Center for EBV/IgA/VCA. The PBMCs will be viably frozen and transported to the LGD at
NCI/FCRDC, where they will be transformed into lymphoblastoid cell lines for extraction of
DNA. At the LGD the DNAs will be screened for informative polymorphisms in candidate genes
by DNA genotyping methods. Association analyses will be performed to detect linkages
between informative polymorphisms in candidate genes by DNA genotyping methods. Association
analyses will be performed to detect linkages between informative polymorphisms and clinical
and family data. If a marker associated with development of NC is found, there are
potential applications in diagnostics and therapy. Further, identification of allelic
polymorphisms in genes with a role in NPC progression would offer definitive ties of such
genes to the carcinogenic process.
Following this study, the samples will be maintained in our repository and curated through
our central Laboratory database. Loss or destruction of these samples wil be recorded in our
database and cannot impact the study participants in any way. We understand that studies
subsequent to the completion of this protocol will require additional OHSR/IRB approval
prior to commencement.
Observational
N/A
Michael Dean, Ph.D.
Principal Investigator
National Cancer Institute (NCI)
United States: Federal Government
999902056
NCT00341146
November 2001
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