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Genetic Susceptibility Loci Identified for Colorectal Tumors

By Labmedica International staff writers
Posted on 03 Mar 2013
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The genetic loci associated with colorectal tumor formation have been identified and could elucidate the mechanisms of pathogenesis.

Over the past several years, genome-wide association studies (GWAS), which focus on common single-nucleotide polymorphisms (SNPs), have successfully discovered low-penetrance loci for colorectal cancer.

A genome-wide association study was conducted that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. Of 2.7 million genetic variants identified, the 10 most statistically significant, previously unreported findings were followed up in six studies; these included 3,056 colorectal tumor cases (2,098 cancers, 958 adenomas) and 6,658 controls of European and Asian descent. The study was led by scientists at Fred Hutchinson Cancer Research Center (Seattle, WA, USA).

The international team uncovered mutations in the following genes which were all genetic variants that previously had not been associated with colorectal cancer: nucleic acid-binding protein (NABP), a gene involved in DNA repair; laminin, gamma 1 (LAMC1), the second gene in the laminin gene family found to be associated with colorectal cancer; cyclin D2 (CCND2), a gene involved in cell-cycle control, which is a key control mechanism to prevent cancer development; and T-box 3 (TBX3), a gene transcription factor that targets a known colorectal cancer pathway.

Ulrike Peters, PhD, MPH, the senior author of the study said, "If a person carries one or two copies of any of these genetic variants, their risk of colorectal cancer is increased by 10% to 40% compared to a person who does not harbor such DNA genetic variants. 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." The study was published online on December 21, 2012, ahead of the April print issue of the journal Gastroenterology.

Related Links:
Fred Hutchinson Cancer Research Center

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