Molecular Genetics Study of Nasopharyngeal Carcinoma: Characterization of NCP Susceptibility Gene(s)
Condition: Nasopharyngeal Carcinoma
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Family-Based
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Chinese population with a high incidence of NPC
      
Keywords: Cancer; Catonese Chinese; Genetic Predisposition; Genotyping; Triad analysis; Nasopharyngeal Cancer; NPC