Colorectal cancer risk variants

31 Mar 2008

New variants affect colorectal cancer risk

Three new variants are associated with increased risk of colorectal cancer, according to two studies published online this week in Nature Genetics. The research also uncovers the first population-specific susceptibility allele for the disease.

Colorectal cancer is the third most common cancer and fourth-leading cause of cancer death worldwide. Lifetime risk in Western European and North American populations is around 5%. Both genetic and environmental factors contribute to the cause of the disease, with about one-third of disease variance attributed to inherited genetic factors. Until very recently, the defined genetic contribution to Colorectal cancer comprised rare, high-penetrance variants in a few genes. However, recent association studies have shown that common genetic variation in the 8q24 and 18q21 (SMAD7)7 regions also contribute to colorectal risk.


The study led by Malcolm Dunlop from the Colon Cancer Genetics Group, at the University of Edinburgh carried out a genome-wide association study of individuals with and without colorectal cancer, and identified a variant on chromosome 11 as increasing risk of the disease by approximately 10%. The variant seems to have a stronger effect on susceptibility to rectal cancer than colon cancer. The authors also observe that Japanese individuals carrying the risk variant do not show an increased risk of colon cancer, although they do have an increased risk of rectal cancer. This is the first report of a population-specific susceptibility allele for colorectal cancer.

In a parallel study, Richard Houlston and colleagues report two new risk loci for the disease on chromosomes 8 and 10. The risk variant on chromosome 8 is near the gene EIF3H, which is known to be overexpressed in other cancers.

For the full paper Dunlop paper see DOI: 10.1038/ng.133
For the full Houlston paper see DOI: 10.1038/ng.111