Molecular Genetics Study of Nasopharyngeal Carcinoma: Characterization of NCP Susceptibility Gene(s)

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00341146
First received: June 19, 2006
Last updated: March 14, 2014
Last verified: May 2013
  Purpose

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.


Condition
Nasopharyngeal Carcinoma

Study Type: Observational
Official Title: Molecular Genetics Study of Nasopharyngeal Carcinoma: Characterization of NPC Susceptibility Gene(s)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 9100
Study Start Date: November 2001
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Individuals must meet the following eligibility criteria to be entered into the NPC study.

Cohort A: Proband: NPC positive (stage III or IV), age less than 50 at time of NPC diagnosis, and EBV/IgA/VCA positive. Spouse of Proband. Child of proband and of spouse (or a parent of the proband)

Cohort B: EBV/IgA/VCA positive 12 years ago and NPC negative. Spouse of proband. Child of proband and of spouse (or a parent of the proband).

EXCLUSION CRITERIA:

Persons with any of the following will be excluded from the study.

Persons who are unwilling or unable to given informed consent, or whose spouse and child(ren) (or parent) are willing to participate and give informed consent/assent.

Persons with no living spouse of child(ren)/parent.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00341146

Locations
China
Institute for Viral Disease Control & Prevention
Beijing, China
Red Cross Hospital Wuzhou City, China
Wuzhou City, China
Sponsors and Collaborators
Investigators
Principal Investigator: Michael Dean, Ph.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00341146     History of Changes
Other Study ID Numbers: 999902056, 02-C-N056
Study First Received: June 19, 2006
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cancer
Catonese Chinese
Genetic Predisposition
Genotyping
Triad analysis
Nasopharyngeal Cancer
NPC

Additional relevant MeSH terms:
Carcinoma
Disease Susceptibility
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on April 15, 2014