Trial Information

Genetic Susceptibility to Oncogenic Viruses

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.