A Study of Molecular and Genetic Factors for Liver Cancer in the Greater Baltimore Area
Condition: Carcinoma, Hepatocellular; Liver Cirrhosis, Alcoholic; Hepatitis, Alcoholic; Hepatitis, Chronic; Hepatitis, Viral, Human
MeSH terms: Hepatitis A; Hepatitis, Viral, Human; Liver Neoplasms; Carcinoma, Hepatocellular; Hepatitis; Liver Cirrhosis; Hepatitis, Chronic; Hepatitis, Alcoholic; Liver Cirrhosis, Alcoholic
Study type: Observational

Summary: 
      Background:

        -  Liver cancer is the third most deadly and fifth most common cancer worldwide.
           Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, and it has
           grown more prevalent in the United States.

        -  More information is needed about the causes and effects of liver cancer, and further
           research into individuals who are at high risk for developing liver cancer is needed for
           early diagnosis and prevention.

      Objectives:

        -  To identify genetic factors that may help to explain the aggressiveness of liver cancer.

        -  To determine if HCC biomarkers exist in blood, urine, and tissue samples.

      Eligibility:

        -  Patients between the ages of 18 and 90 who have been diagnosed with HCC or have a high
           risk for developing HCC because of fatty liver disease (alcohol-related or
           non-alcohol-related) or chronic hepatitis B or C.

        -  Participants will reside in Baltimore City and the surrounding areas.

      Design:

        -  Participants will complete a questionnaire and provide blood and urine samples for
           testing:

        -  The questionnaire will include questions about individual and family medical history,
           tobacco use, and exposure to known factors for liver cancer.

        -  Blood and urine samples will be collected from all participants after the questionnaire.

        -  Tumor tissue and healthy tissue will be collected from selected participants if they
           undergo surgery for their cancer or disease.

        -  No specific treatment will be offered as part of this protocol, but participants have
           the option to be treated under different protocols.
    

Detailed description: 
      BACKGROUND:

      Liver cancer is the third most deadly and fifth most common cancer worldwide. Hepatocellular
      carcinoma (HCC) is the most frequent primary cancer of the liver with rising incidence in the
      United States. HCC patients have a dismal outcome and are an underserved cancer population.
      We are proposing a liver cancer case-control and case-case study to be conducted in
      Baltimore, Maryland.

      OBJECTIVES:

      Our research is aimed to identify genetic and genomic changes that might explain the
      aggressive nature of liver cancer. We will test the primary hypothesis that HCC biomarkers
      exist in blood products (or mouth wash), urine and/or tissues that can be used for early
      diagnosis and prevention. A unique study factor is the use of urine samples for biomarker
      identification. A secondary goal will be to examine whether certain genetic and genomic
      factors modify liver cancer susceptibility using candidate and genome wide association study
      approaches. Although other studies have investigated genetic susceptibility, large scale
      studies have not been conducted for liver cancer. Our study will also be valuable due to
      access to frozen tumor specimens from pre-therapy resection, whose collection is required for
      gene expression analysis. If certain genes are related to HCC risk and progression, this
      tissue resource will be used to further validate our findings with laboratory investigations.
      The proposed study is designed to be exploratory and hypothesis generating.

      ELIGIBILITY:

      The participants will reside in Baltimore City and surrounding areas. Cases will have
      pathologically confirmed liver cancer or risk factors for HCC development. Risk factors
      include chronic liver disease due to hepatitis B and/or C viral infection, nonalcoholic
      steatohepatitis or alcoholic cirrhosis. The study will be supported by an epidemiological
      infrastructure developed by our University of Maryland School of Medicine resource contractor
      for ongoing lung and prostate cancer case-control studies. The enrollment of controls will
      begin concurrently with case accrual, and will continue for 5 years. Population-based
      controls will be recruited using a triple eligibility criterion, such that controls eligible
      for the lung/prostate study will be asked to complete a supplemental questionnaire for the
      liver study.

      DESIGN:

      The study will include 400 primary HCC cases, 800 patients with chronic liver disease (high
      risk non-cancer cases) and a sample of 800 population-based controls. The HCC and high risk
      non-cancer cases will be recruited at two Baltimore hospitals, the Veterans Affairs Medical
      Center, and the University of Maryland School of Medicine over a period of 13-15 years.
      Controls will be identified through a Department of Motor Vehicle database and match cases by
      age, gender, race and county of residency. The study will involve administration of a
      questionnaire and collection of blood (or mouth wash) from all study subjects. Fresh-frozen
      tumor and tumor surrounding non-cancerous specimens will be obtained from approximately 20
      percent of the cancer patients. The cases will receive one questionnaire.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study will include 400 primary HCC cases, 800 patients with chronic liver disease (high
        risk non-cancer cases) and a sample of 800 population-based controls. The HCC and high risk
        non-cancer cases will be recruited at two Baltimore hospitals, the Veterans Affairs Medical
        Center and the University of Maryland School of Medicine over a period of 13 - 15 years.
        Controls will be identified through a Department of Motor Vehicle database and match cases
        by age, gender, race and county of residency.
      
Biospecimen description: 
      Blood and tissue samples, mouth wash and urine.
    
Keywords: Hepatocellular Carcinoma; Liver Cancer; Chronic Liver Disease; Genome Wide Association Study; Gene Expression Profiling