A Study of Molecular and Genetic Factors for Liver Cancer in the Greater Baltimore Area
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.
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.
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.
The study will include 250 primary HCC cases, 500 patients with chronic liver disease (high
risk non-cancer cases) and a sample of 500 population-based controls. The HCC and high risk
non-cancer cases will be recruited at three Baltimore hospitals, the Veterans Affairs
Medical Center, the University of Maryland School of Medicine and the Johns Hopkins Medical
Institute, over a period of 5 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. The first 12 months will constitute a pilot study, during which
we will evaluate and refine recruitment procedures.
Time Perspective: Prospective
Xin Wang, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|University of Maryland Medical Center||Baltimore, Maryland 21201-1595|
|Johns Hopkins University Medical Center||Baltimore, Maryland 21205|
|Veterans Affairs Medical Center||Baltimore, Maryland|