BioWorld International Correspondent
LONDON - A common genetic variant that puts people at greater risk of colorectal cancer has been found on a region of chromosome 8 that is, intriguingly, already known to be linked to prostate cancer.
The variant, a single nucleotide polymorphism (SNP), is present in about half of the European population and causes a 20 percent increase in the risk of developing colorectal cancer. The lifetime risk of developing the disease rises from around 1 in 20 for people who do not have the variant, to 1 in 16 for those who do.
Richard Houlston, professor of molecular and population genetics at the Institute of Cancer Research in Sutton, UK, told BioWorld International, "This study provides unequivocal evidence that common variation is a contributing factor to inherited predisposition to colorectal cancer. Before this, we had assumed that inherited predisposition was largely confined to rare mutations that conferred substantial risk, but this finding has caused a paradigm shift."
The area where the variant was found, on chromosome 8q24, is in a "gene desert," Houlston said. "It is obviously having an effect on the expression of something, but we don't know what that is at the moment," he added.
Houlston and his colleagues used the same method, known as a genome-wide association scan, to identify the SNP as the researchers who reported earlier this year that they had identified five genes that may account for 4 percent of inherited cases of breast cancer. (See BioWorld International, May 30, 2007.)
As in the earlier trawl for breast cancer genes, Houlston's team aimed to identify SNPs that were inherited more commonly by people with colorectal cancer than by healthy controls.
Cancer Research UK funded both studies. The charity is launching similar genome-wide searches for variants linked to lung and ovarian cancer, in the hope of identifying genes that will be useful for screening purposes or that will lead to new therapeutic strategies.
There are estimated to be more than 7 million common SNPs in the human genome, but because recombination generally takes place at particular "hotspots," many of the SNPs commonly are inherited together. Researchers therefore can use a panel of SNPS (known as tags) to infer which groups of SNPs have been inherited by people with colorectal cancer and which by healthy controls.
Further investigation of stretches of the genome that are inherited most commonly by people with disease and not by healthy controls then can help scientists to pinpoint variations such as mutations and SNPs.
Houlston and his colleagues reported their findings in a paper in the July 8 issue of Nature Genetics titled: "A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21.".
There are two companion papers in the same issue of Nature Genetics. The first, by Brent Zanke of Cancer Care Ontario, Canada, and collaborators is titled: "Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24." That study also was partly funded by Cancer Research UK.
As the title suggests, the researchers independently found a region on the long arm of chromosome 8 where a common variant is associated with a higher risk of bowel cancer.
The second paper, by Christopher Haiman of the University of Southern California, and collaborators, is titled: "A common genetic risk factor for colorectal and prostate cancer." The scientists looked at five variants on chromosome 8q24 already shown to increase the risk of prostate cancer, and found that only one - the same one as identified by Houlston and colleagues - was significantly associated with colorectal cancer.
They concluded that the mechanism by which those variants contribute to increased cancer risk may vary, depending on the type of cancer.
In Houlston's study, the researchers started by genotyping more than 550,000 SNPs in 930 people with an inherited form of colorectal cancer and 965 controls. SNPs on chromosome 8q24 seemed to be associated with colorectal cancer and, Houlston noted, "one of these stuck out like a sore thumb." Further investigations in other datasets confirmed the importance of this SNP.
Those researching genetic variants linked to increased risk of breast, prostate and colon cancer currently are discussing how best to take work on chromosome 8 forward to the next stage.