LONDON (Reuters) - Scientists have found how a single variant in a person's genetic code can lead to the development of bowel cancer and say their work should help in creating new drugs to combat the disease.
An international study led by researchers at Britain's Institute of Cancer Research (ICR) found that if people have a single letter change in their DNA code at a gene variant called rs16888589, they produce more protein from a gene called EIFH3.
The team also showed that having high levels of the EIFH3 protein leads to the development of bowel cancer -- a disease that kills around half a million people each year and is the second most common cause of cancer death in the world.
"It's interesting that even a single change to the DNA sequence can alter how much protein is produced and increase the risk of this disease. Finding proteins involved in cancer development is crucial, as they are potential targets for new drugs," said the ICR's Richard Houlston, whose work was published in the Public Library of Science Genetics journal.
"We know from other cancers that too much of the protein EIFH3 leads to an increase in cell proliferation, growth and survival, but this is the first confirmation it is involved in bowel cancer development."
Previous studies known as genome-wide association studies, which scan gene maps, have identified 14 DNA variants that each increase the risk of bowel cancer by between 1.5 and 2 times.
These variants, called single nucleotide polymorphisms (SNPs), are a single letter change in the DNA code -- the sequence of letters that makes up a person's genetic blueprint.
Houlston's team wanted to find which of these variants are not only associated with bowel cancer, but cause it. There are likely to be several causative variants among the 14, they said.
In their study, they screened 2,000 people with bowel cancer and 2,000 people without the disease and found four SNPs that stood out. All were near a gene called EIFH3, and further research showed how one of them, called rs16888589, caused a change in the amount of protein produced by EIFH3.
"This study is another important step toward understanding the gene faults that put some people at greater risk of bowel cancer, and it also gives us clues to how the disease develops," said Lesley Walker, science information director at the charity Cancer Research UK, which part-funded the study. "Research like this opens up possibilities for developing new treatments that target cancers with particular genetic faults."
Roche's Xeloda and Sanofi-Aventis' Eloxatine are among leading drugs licensed for the treatment of bowel cancer, often referred to as colorectal or colon cancer.
A separate study in Thursday's Gut journal, a British Medical Journal title, found that taking the painkiller aspirin regularly can help protect people against colon cancer even if it is taken at the lowest possible dose of 75 milligrams (mg) a day. The findings back previous results showing that aspirin can ward off bowel cancer.
Scientists found that taking 75mg of aspirin every day for one to three years led to a 19 percent reduction in risk of developing bowel cancer, while taking it daily for three to five years led to a 24 percent reduced risk. The risk reduction rose to 31 percent for people taking the drug for five to 10 years.
SOURCES: http://link.reuters.com/duw34p PLoS Genetics, Vol. 6, No. 9, September 16, 2010 and http://link.reuters.com/fuw34p Gut, online September 15, 2010.
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