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Genome-wide Association Study Reveals 40 new Genetic Links to Colorectal Cancer
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A genome-wide analysis of more than 100,000 individuals identified 40 new genetic variants that point to an increased risk for colorectal cancer, according to research published in Nature Genetics.
Jeroen Huyghe, PhD, of Fred Hutchinson Cancer Research Center, said the discovery of these variants — and the validation of 55 previously identified variants — could spur new personalized screening strategies and reveal new targets for drug development.
“There's great potential in using [genome-wide association study (GWAS)] results to inform target discovery for anti-cancer drugs. For diseases like type 2 diabetes and heart disease, the GWAS approach drives the discovery of new biology and potential drug targets,” Huyghe said in a press release. “To date, the search for new targets for cancer therapy has been limited to focus primarily on the molecular characteristics of cancer cells. We think there is a huge opportunity in using the GWAS approach to inform drug development for colorectal cancer.”
Investigators began their study by performing whole-genome sequencing of 1,439 cases and 730 controls. Then, they tested any discovered sequence variants in a GWAS for association in 34,869 cases and 29,051 controls. They followed up their findings in an additional 23,262 cases and 38,296 controls.
A meta-analysis of 125,478 individuals revealed 40 new independent signals for CRC, which brings the number of independent signals for CRC to nearly 100, researchers said. Additionally, they discovered a strongly protective 0.3% frequency variant signal at CHD1, the first protective variant identified for sporadic CRC.
“Large-scale whole-genome sequencing studies have discovered millions of genetic variants that have yet to be examined systematically for association with disease,” Huyghe said in the release. “Our research capitalized on the availability of the Haplotype Reference Consortium panel, a population reference panel of sequence data from more than 32,000 individuals. By coupling this strategy with a custom-designed genotyping chip, we were able to robustly identify a rare variant association signal and multiple additional signals involving lower-frequency variants.”
The next step for this team of researchers involves expanding the study population to make it more diverse. Investigators acknowledged that their study was mostly made of individuals of European descent, which could lead to bias in the results.
“It is critically important that we increase diversity in our future studies because premature use of these findings to inform screening guidelines could exacerbate existing racial disparities in colorectal cancer screening and survival rates,” Stephanie Bien, PhD, staff scientist at Fred Hutchinson said in the press release. – by Alex Young
Disclosures: Huyghe and Bien report no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.
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Huyghe JR, et al. Nat Genet. 2018;doi:10.1038/s41588-018-0286-06.
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