Hutch News

Four gene variants associated with increased colorectal cancer risk identified

Fred Hutchinson Cancer Research Center’s Riki Peters, Li Hsu lead international genomewide-association study, pointing to potential drug targets, top screening beneficiaries

Feb. 25, 2013
Drs. Ulrike Peters and Li Hsu, Public Health Sciences Division

Drs. Ulrike Peters and Li Hsu, Public Health Sciences Division

An international research team co-led by cancer prevention researcher Dr. Ulrike "Riki" Peters and biostatistician Dr. Li Hsu of the Public Health Sciences Division has identified variations in four genes linked to an increased risk of colorectal cancer. Peters and colleagues from 40 institutes throughout the world published their findings online ahead of the April print issue of Gastroenterology.

For the past four years, Peters and colleagues have been studying the genes linked to colorectal cancer through the  Genetics and Epidemiology of Colorectal Cancer Consortium, a collaboration involving researchers from North America, Australia and Europe who have pooled data from approximately 40,000 study participants, about half of whom have colorectal cancer. The Hutchinson Center houses GECCO’s coordinating center and Peters is its principal investigator.

The genomewide-association study was conducted in two phases. The first involved rapidly scanning complete sets of blood DNA from 12,696 people with colorectal cancer or a precancerous condition called adenoma. This data was then compared to the same set of variants from 15,113 healthy controls of European descent.

Of 2.7 million genetic variants identified, the 10 most statistically significant mutations associated with colorectal cancer were then further analyzed in a follow-up genomewide-association study of 3,056 colorectal cancers or adenomas and colon-tissue samples from 6,658 healthy controls of European and Asian descent.

The research team uncovered mutations in the following genes—all genetic variants that previously had not been associated with colorectal cancer:

  • NABP – a gene involved in DNA repair
  • LAMC1 – the second gene in the laminin gene family found to be associated with colorectal cancer
  • CCND2 – a gene involved in cell-cycle control, which is a key control mechanism to prevent cancer development
  • TBX3 – a gene transcription factor that targets a known colorectal cancer pathway

If a person carries one or two copies of any of these genetic variants, their risk of colorectal cancer is increased by 10 percent to 40 percent compared to a person who does not harbor such DNA genetic variants, Peters said.

"These findings could potentially lead to new drug targets and, in combination with previously identified genetic and environmental risk factors, identify subgroups of the population that can benefit most from colorectal-cancer screening and could be targeted for early or more frequent endoscopy, a very effective screening tool for colorectal cancer," said Tabitha Harrison, a co-author on the paper and the GECCO project manager.

Other co-authors from Fred Hutch included statistical research associate Conghui "Flora" Qu and staff scientist Dr. Shuo Jiao, both of PHS.

The National Cancer Institute, the National Institutes of Health and the U.S. Department of Health and Human Services funds GECCO.


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