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Colorado Researchers Find Different Genetic Drivers of Colorectal Cancer in Old and Young

NEW YORK (GenomeWeb) – Researchers from the University of Colorado Cancer Center have conducted a pilot study to understand the genetic differences between colorectal cancer in young and old patients and try to explain worse outcomes in the former group.

Overall the rate of colorectal cancer is declining, but the rate of young patients with the disease is increasing. Previous studies have shown that colorectal cancer in patients younger than 50 years tends to be more aggressive than it is in older patients.

In the study, being presented this weekend at the Gastrointestinal Cancers Symposium in San Francisco, the researchers compared nine tumors from younger patients (median age 31) and nine tumors from older patients (median age 73). The investigators extracted total RNA from the tumor tissues and sequenced them on the Illumina HiSeq 2000. They obtained 45 million reads from each of the tested tumors that they mapped to a reference genome using the Bowtie Genome Index.

The reads showed 141 genes that are enriched in samples from younger patients and a largely different cohort of 42 genes enriched in samples from older patients. Many of the enriched genes in samples from younger patients are involved in signaling pathways such as ERBB2, NOTCH3, and CAV1, which are known to spur cell proliferation commonly associated with cancer. In contrast, pathways enriched in samples from older patients included CDX2, HMGB3, and EPHB2, which are primarily involved in cell differentiation.

The researchers believe that the enrichment of ERBB2 (Her2/neu) in samples from younger patients is an especially interesting target, since there are US Food and Drug Administration-approved therapies that target this particular gene.

The team plans to validate the differences in a larger patient population. "If I were to shoot for the stars, I would say that our end goal is to be able to offer better treatments for this population of young colorectal cancer patients that seem to be at higher risk from the disease," Chrisopher Lieu, investigator at the CU Cancer Center, assistant professor of medical oncology at the University of Colorado School of Medicine, and first author on the study, said in a statement.

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