Genetic Susceptibility to Oncogenic Viruses
Condition: Liver Neoplasms; HIV Infections
MeSH terms: Liver Neoplasms; Genetic Predisposition to Disease
Study type: Observational

Summary: 
      An NCI goal is to identify every human gene that predisposes people to cancer. Recent studies
      of HIV-1 indicate that genetic polymorphisms can affect susceptibility to viral infections
      and that such alleles may be racially restricted, a range of racial and ethnic groups should
      be included in such studies. We propose to examine genetic determinants of infection with
      hepatitis B virus (HBV) and hepatitis C virus (HCV) in an ethnically diverse population of
      injection drug users (IDUs). HBV and HCV are important causes of hepatocellular carcinoma,
      but little is known about genetic factors that alter susceptibility to these infections.
      Subjects will be recruited in diverse inner-city neighborhoods as part of the University of
      California, San Francisco's Urban Health Study. Since 1986, this study has successfully
      recruited and evaluated IDUs from street-based settings. About half of the participants are
      African-American, one-third are white, 10% are Latino, and the remainder are Asian or Native
      American. The mean duration of drug use exceeds 20 years. About 80% of subjects have evidence
      of HBV infection and a similar prevalence of HCV infections is anticipated. We will enroll
      about 1500 subjects over a 13 month period. Archived, unlinked serum specimens may be
      obtained from previous enrollees to increase the sample size, as needed. Highly
      exposed-uninfected subjects will be ascertained on the basis of the serologic testing for
      each virus, as well as the duration and frequency of injection drug use. These highly
      exposed-uninfected subjects will be compared to infected subjects with regard to their
      frequency of genetic polymorphisms (chemokines, chemokine receptors, human leukocyte
      antigens, and others), in collaboration with scientists from NCI's Laboratory of Genomic
      Diversity.
    

Detailed description: 
      An NCI goal is to identify every human gene that predisposes people to cancer. Recent studies
      of HIV -1 indicate that genetic polymorphisms can affect susceptibility to viral infections
      and that such alleles may be detected in studies of small numbers of highly
      exposed-uninfected subjects. Because such alleles may be racially restricted, a range of
      racial and ethnic groups should be included in such studies. We propose to examine genetic
      determinants of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in an
      ethnically diverse population of injection drug users (lDUs). HBV and HCV are important
      causes of hepatocellular carcinoma, but little is known about genetic factors that alter
      susceptibility to these infections. Subjects will be recruited in diverse inner-city
      neighborhoods as part of the University of California, San Francisco's Urban Health Study.
      Since 1986, this study has successfully recruited and evaluated IDUs from street-based
      settings. About half of the participants are African-American, one-third are white, 10% are
      Latino, and the remainder are Asian or Native American. The mean duration of drug use exceeds
      20 years. About 80% of subjects have evidence of HBV infection and a similar prevalence of
      HCV infection is anticipated. We will enroll about 1500 subjects over a 13 month period.
      Archived, unlinked serum specimens may obtained from previous enrollees to increase the
      sample size, as needed. Highly exposed-uninfected subjects will be ascertained on the basis
      of the serologic testing for each virus, as well as the duration and frequency of injection
      drug use. These highly exposed-uninfected subjects will be compared to infected subjects with
      regard to their frequency of genetic polymorphisms (chemokines, chemokine receptors, human
      leukocyte antigens, and others), in collaboration with scientists from NCI's Laboratory of
      Genomic Diversity.
    

Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Residents of inner-city neighborhoods in San Francisco, CA.
      
Keywords: Genetics; Liver Cancer; HIV