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Hutchinson Cancer Center Wins $13M for Colorectal Cancer GWAS Consortium

NEW YORK (GenomeWeb News) – Fred Hutchinson Cancer Research Center scientists will use a $13 million award from the National Cancer Institute to fund a consortium that will use genome sequencing and genome-wide association study data to identify rare genetic variants that may be involved in colorectal cancer.

Ulrike Peters, a member of the Hutchinson Center's Public Health Sciences Division, will lead the effort, which also will involve partners through the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), for which Peters is principal investigator.

Peters and her GECCO partners over the past four years have studied data from 40,000 participants, approximately half of whom have CRC, using genotyping to identify some of the most common genetic variants and mutations involved in CRC. The researchers will now use next-generation sequencing to capture more rare variants and genetic irregularities that could be involved in heritable CRC cases.

The hope is that by finding and adding rare variants to the knowledge base of more common ones it will be possible to help more people with the disease, lead to a better understanding of how CRC develops, and inform development of new drugs.

In addition, Peters and her partners now have formed the Colorectal Cancer GWAS Consortium, which aims to conduct a pooled analysis of all five existing CRC genome-wide association studies – which involve over 6,500 CRC cases and over 9,000 controls. They plan to use the NCI funding to validate the consortium's findings about promising genetic variants in a large-scale replication study. This second study will involve around 8,500 CRC cases and around 11,500 matched controls from 11 well-described populations.

In the replication study, Peters and her colleagues also will genotype 7,600 variants with the expectation of finding several highly significant novel CRC susceptibility genes or loci.

"This is an important step, to look at much of the genetic variation across the entire genome. We didn't have the opportunity to study this in the past with the technologies we had before," Peters said in a statement.

"We are now able to investigate millions of common and rare variants across the genome. Next-generation sequencing is becoming more readily available to look at these variants on a large scale," she added.

CRC kills more than 50,000 Americans each year, and about one-third of these cases may be attributable to heritable causes and involve genetic mutations that affect a person's susceptibility to increased CRC risk.

To date, Peters and other researchers have identified around 20 common genetic links to CRC, which account for around 8 to 10 percent of CRC cases.

"Our new grant will allow us to identify some of the missing heritability that has not been found so far," Peters said.