People who have lower levels of a certain enzyme in their body may be more susceptible to developing cancer of the liver, says a group of medical researchers.1 That's the hypothesis. So far, it's only been tested in animals.
Tracing Back to an Abnormal Gene
Doctors at Mount Sinai Hospital, affiliated with the University of Toronto, reached their findings from a study using mice that were born with lower levels of an enzyme known as Plk4. These mice were intentionally bred to carry a missing copy of the gene that prompts the enzyme's activity in the body.
"Our study indicates that loss of one copy of Plk4 is a major risk factor for primary liver cancer," explained Carol Swallow, MD, PhD, a surgical oncologist at Mount Sinai Hospital in Toronto, who headed the research.
Liver Cancer was the Most Common Found
In the mice used in the study, Swallow and her associates learned that when only half the normal amount of the enzyme was present, the rodents faced a higher risk of developing liver cancer. This was one of the first studies, the researchers stressed, that evaluated the genetic basis behind the origins of liver cancer.
While the mice with lower levels of the enzyme "show no obvious defects early in life", the researchers had theorized that it might predispose them to developing cancer as they aged. As they expected, "elderly Plk4 [deficient] mice developed grossly apparent tumors at a frequency of 50 percent (30 of 59) at a variety of sites, compared with only 3 percent (1 of 31) of Plk4 [deficient] littermates," Swallow's team wrote.
The most common site of tumor development was in the livers of these animals, they reported, and most of the lesions seen were those of primary hepatocellular carcinoma, the most common form of liver cancer.
When the team studied the liver cells of mice with less Plk4, they found "poorly organized" and significantly misshaped cells compared to those of mice that had normal levels of the enzyme.
Patient Implications
They believe the findings have significant implications in terms of screening patients for liver cancer, as well as early detection of the disease. The findings would have to be confirmed in humans first before tests to look for the enzyme could be developed as part of a screening process.
The role of the Plk4 enzyme may be significant in people with hepatitis B or C infection, as well, Swallow and her colleagues wrote. Proteins produced by the hepatitis virus suppress genes that normally help prevent cancer formation in the body,2 they stated, and in cases of reduced Plk4 function, the ability of these viruses to promote cancer development "should be enhanced".
Origins of Liver Cancer
Cases of liver cancer in the United States continue to rise each year, according to estimates. This is a type of cancer that begins directly in the cells of the liver. It is also prone to spread to other parts of the body. The exact causes of liver cancer aren’t known, but researchers believe the cancer begins when DNA is damaged. This material contains instructions on the rate of cell growth in the liver. When it is damaged, cells in the liver grow out of control and eventually form a tumor.
Factors known to damage DNA in liver cells include infection with either hepatitis B or C, liver cirrhosis, long-term exposure to certain chemical carcinogens, an inflammation of the liver's bile ducts known as primary biliary cirrhosis, and an inflammatory condition known as ulcerative colitis.
No completely accurate screening test is available today for liver cancer. However, doctors sometimes use a blood test that looks for a biomarker known as alpha fetoprotein (AFP), a type of protein not normally found in adults. Malignant liver tumors are known to produce AFP. Other screening tests include ultrasonography, a CT screening, magnetic resonance imaging (MRI), or a liver biopsy.3
Liver Cancer Prevalence Around the World
According to the American Cancer Society, there will be 667,000 new cases of liver cancer diagnosed this year alone, with 83% of these cases occurring in developing countries, particularly in Southeast Asia. The disease is also more prevalent in men compared to women, experts say.
The discovery that there's an apparent association between liver cancer susceptibility and the Plk4 enzyme "represents a major advance in our understanding of [liver cancer] at a molecular level, and provides insight into who may be predisposed to this type of cancer genetically," Swallow explained.
1. Ko MA, Rosario CO, Hudson JW et al. Plk4 haploinsufficiency causes mitotic infidelity and carcinogenesis. Nat Genet 2005 Aug;37(8):883-8. Epub 2005 Jul 17.
2. Brechot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 2004 Nov;127(5 Suppl 1):S56-61.
3. Liver Cancer Overview. Mayo Foundation for Medical Education and Research. Available at: http://www.mayoclinic.com/invoke.cfm?objectid=C2850661-4805-4AD6-905AD30E9FC79DB2&dsection=1. Accessed September 2, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
