STANFORD RESEARCHER IDENTIFIES GENES POINTING TO LIVER CANCER; ADVOCATES SCREENING FOR ASIAN POPULATIONS

6/4/02
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STANFORD RESEARCHER IDENTIFIES GENES POINTING TO LIVER CANCER; ADVOCATES
SCREENING FOR ASIAN POPULATIONS
STANFORD, Calif. - Cancerous liver cells rely on a different set of genes
than normal liver cells in order to function. Now researchers at Stanford
University Medical Center have identified genes needed by cancerous liver
cells but ignored or used at different levels by normal liver cells. This
discovery could lead to more effective treatments and screening tests for
liver cancer, which is usually not detected until the disease is too
advanced to treat effectively. A screening test would be of particular
benefit to Asian and Pacific Island populations, which have roughly 10 times
the risk of liver cancer than Caucasians because of high rates of chronic
hepatitis B infection.
There's a real opportunity to use this information to develop better and
cheaper tests for diagnosis and treatments," said Samuel So, MD, director of
Stanford's Asian Liver Center and an associate professor of surgery at the
School of Medicine. Last year, So launched the Jade Ribbon Campaign to draw
attention to the high rate of hepatitis B among Asian Americans. Chronic
hepatitis B infection can lead to liver cancer.
Surgically removing the tumor is considered the only effective treatment for
liver cancer, but less than 20 percent of liver cancer patients are
diagnosed when surgery is still an option. Of those who undergo surgery, 50
percent experience a relapse. "Most of the time, if you wait until the
patient has symptoms, the diagnosis is too late," said So, who also oversees
the medical center's liver cancer program. Because of late discovery, he
added, many liver cancer patients survive only four to six months after
diagnosis.
To identify the genes in this study, So and his colleagues compared the
genes being used in more than 200 normal and tumor samples. First they
isolated RNA from the samples (RNA is produced by active genes - the more
active the gene, the more RNA is produced). Then they tacked a fluorescent
molecule onto the RNA and washed it over the surface of a glass slide dotted
with 17,400 human genes. Any RNA that corresponded to a gene on the array
stuck, creating a fluorescent spot. A brighter spot meant more RNA and more
gene activity.
By comparing the pattern of fluorescent spots created by both normal and
tumor samples, the researcher determined which genes were being used at
either high or low levels in the tumor samples. They reported these findings
in the June issue of the journal Molecular Biology of the Cell. Many of the
genes they found were well-known cancer genes; however, "many were not known
to play a role in liver cancer," So said. Of these, he hopes to find genes
that make proteins that are secreted from the tumor and are present in the
bloodstream of individuals with liver cancer.
"If that protein is only present or produced in high levels in people with
liver cancer, maybe we can develop a better blood test to detect the
cancer," So said. He added that other proteins could be targets for new
drugs to treat the disease once it's diagnosed.
So said many Asians are exposed to hepatitis B at birth and roughly 10 to 15
percent become chronic carriers of the disease. Overall, 400 million people
worldwide have chronic hepatitis B. Although infected individuals may feel
healthy, the disease can cause scarring of the liver (cirrhosis) or liver
cancer in people as young as 30. So recommends that all Asian Americans be
screened for hepatitis B and get vaccinated if they test negative.
Hepatitis B carriers should be screened for liver cancer every six months by
having their blood tested for a protein called alpha-fetoprotein, which is
sometimes at higher levels in people with liver cancer. These individuals
also should undergo a liver ultrasound annually to look for tumors. So said
neither technique is completely accurate nor are the precautions inexpensive
enough for widespread use in poor countries, highlighting the need for a
better screening tool.
So's colleagues include Xin Chen MD, PhD, research associate at the Asian
Liver Center and the department of surgery; Pat Brown MD, PhD, professor of
biochemistry; David Botstein, PhD, professor of genetics; Chris Barry, MD,
PhD, resident in surgery; and his collaborators from the University of Hong
Kong. Other Stanford investigators are John Higgins, MD, assistant professor
of pathology; Matt van de Rijn, MD, PhD, associate professor of pathology;
and Kin-man Lai, MD, resident in surgery.
Stanford University Medical Center integrates research, medical education
and patient care at its three institutions - Stanford University School of
Medicine, Stanford Hospital & Clinics and Lucile Packard Children's
Hospital. For more information, please visit the Web site of the medical
center's Office of News and Public Affairs at http://mednews.stanford.edu.
http://mednews.stanford.edu/news_releases_html/2002/junereleases/liver_cance
r.html