New Susceptibility Loci for Colorectal Cancer Identified by Genome-Wide Association Studies on East Asians

A genome-wide association study (GWAS) conducted on individuals from several East Asian countries identified four genetic foci linked to colorectal cancer, three of which were also found in a population of European descent.

A GWAS is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait. A GWAS typically focuses on associations between single-nucleotide polymorphisms (SNPs) and traits such as major diseases. These studies normally compare the DNA of two groups of participants: people with the disease (cases) and similar people without (controls). Each person gives a sample of DNA, from which millions of genetic variants are read using SNP arrays. If one type of the variant is more frequent in people with the disease, the SNP is said to be "associated" with the disease. The associated SNPs are then considered to mark a region of the human genome, which influences the risk of disease. In contrast to methods that specifically test one or a few genetic regions, a GWAS investigates the entire genome. A GWAS identifies SNPs and other variants in DNA, which are associated with a disease, but cannot on its own specify which genes cause the illness.

In a paper published in the December 23, 2012, online edition of the journal Nature Genetics investigators at Vanderbilt University (Nashville, TN, USA) searched for new genetic factors associated with colorectal cancer (CRC) by conducting a GWAS on an East Asian test group comprising 2,098 cases and 5,749 controls. From this group they selected 64 promising SNPs for replication in an independent set of samples, including up to 5,358 cases and 5,922 controls. Results of the second study yielded four foci linked to CRC. Three of the four were replicated in a study conducted in 26,060 individuals of European descent.

"Looking at different ethnic groups is important because the genetic structures can be different enough that variants identified in one population do not explain risk in other populations," said senior author Dr. Wei Zheng, professor of cancer research at Vanderbilt University. "Because of the difference in genetic structures and underlying environment exposures, it might be easier to discover some risk variants in studies conducted in non-European populations."

"The findings from this study are relevant to both Asian and European populations," said Dr. Zheng. "Interestingly, these three susceptibility loci were not discovered in previous studies conducted in European-ancestry populations. These new discoveries are very exciting. They will certainly lead to future studies regarding the biology of these regions and the translational potential of these findings in cancer prevention and treatment."

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