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Digging for DNA that Drives Colon Cancer

10 July 2007 (All day)
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Three independent groups have hit on the first common genetic variant that appears to raise the risk of colorectal cancer, albeit by a small amount, and which they estimate is found in half the world's population. Although rare genes have been linked to the disease before, this is the first evidence of common DNA--and also notable because it falls outside a gene, in so-called "junk DNA."

Colorectal cancer appears to run in families to some degree, but scientists have been frustrated in their hunt for common genes that might spur it. Now, three groups separately identified a chromosomal region that doesn't contain any known genes, but that has been previously linked to both prostate and breast cancer.

One study, headed by geneticists Malcolm Dunlop of Western General Hospital in Edinburgh, U.K., and Thomas Hudson of the Ontario Institute for Cancer Research in Toronto, Canada, turned to DNA from almost 14,000 people with colorectal cancer, along with roughly the same number of people without the disease, all from various parts of North America and Europe. They examined nearly 100,000 single-nucleotide polymorphisms (SNPs)--single DNA bases that vary between individuals--searching for any that might be more common in those with the disease.

A second team, headed by Richard Houlston at the Institute of Cancer Research in Sutton, U.K., took a similar approach, scanning more than 500,000 SNPs in 930 people with colon cancer who had a family history of the disease and 960 people without colon cancer. Just like the first group, they found that a particular SNP in a region of chromosome 8 was linked to a 20% or so increased likelihood of the disease. Repeating the genome scans in more than 7000 Europeans with colon cancer and more than 5000 without, the same SNP popped up.

The third team, led by epidemiologist Christopher Haiman at the University of Southern California in Los Angeles, had taken a more focused approach from the start, intrigued by the DNA region's known association with prostate cancer. The researchers turned to DNA samples from a mix of ethnicities, including African-Americans, Japanese-Americans, Latinos, and European Americans; about 1800 had had colon cancer and 5500 were healthy. Like the first two groups, this one found the same association with the disease. Because the SNP is in a region with no known genes, known colloquially as "junk DNA," Haiman says, it may offer useful clues about the role of this still-mysterious DNA that litters our genome.

The SNP is not necessarily the culprit, but may be inherited with DNA nearby that is. Exactly how this DNA region might affect colorectal cancer isn't yet clear; the SNP also only increases risk somewhat, by just over 20% in these studies. This means that someone with a 6% lifetime risk of colon cancer--the average in the U.S.--for example, would have a 7.2% risk if they carried the deleterious SNP. But Houlston's group also found an association between the strip of DNA and colorectal adenomas, which precede tumors--suggesting, his team believes, that the variant might help initiate cancer rather than drive its progression. All three studies appeared together online 8 July in Nature Genetics.

Although clinical applications may be a ways off, the new marker may someday help identify those at risk of colon cancer and even guide physicians to patients in the early stages of the disease. "This could be really useful," says molecular geneticist Bert Vogelstein of Johns Hopkins University in Baltimore, Maryland. Colon cancer can usually be cured if detected early, he says. The variant might also offer researchers clues about "how genes become abnormal" and help drive cancer more generally, says Dunlop.

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