Study finds many patients with family history of LINE-1 hypomethylated colorectal cancer

Published on December 13, 2012 at 1:07 AM · No Comments

When people with a family history of colorectal cancer develop the disease, their tumors often carry a molecular sign that the cancer could be life-threatening and may require aggressive treatment, Dana-Farber Cancer Institute scientists report in a new study.

The finding, reported in the Journal of the National Cancer Institute, draws on data from studies that have tracked the health of tens of thousands of people over several decades. It suggests that colorectal cancer patients could one day have their tumor tissue tested for the molecular sign, and, if necessary, receive more powerful therapies and a familial cancer-risk assessment for their relatives. It further suggests that such patients' relatives could be eligible for more frequent colonoscopies to catch the disease at the earliest possible stage.

Unlike other abnormalities that raise the risk of colon cancer in some families, the newly discovered sign is not linked to a gene mutation that can be inherited from one's parents or grandparents. It appears in DNA segments that are thought to have entered the human genome millennia ago, possibly through infection by retroviruses. These sections, known as long interspersed nucleotide element 1 (LINE-1), are sprinkled throughout the human genome and make up about 17 percent of our DNA. Normally, LINE-1 doesn't cause much trouble, because it's blanketed by methyl groups (packets of one carbon atom bound to three hydrogen atoms).

In the current study, researchers led by Dana-Farber's Shuji Ogino, MD, PhD, MS, and Charles Fuchs, MD, MPH, found that for many colorectal cancer patients with a family history of the disease, the LINE-1 in their tumor cells was nearly bare of methyl groups (a condition known as hypomethylation).

"Previous studies have suggested that some colorectal cancers exhibit an instability of the epigenome, the cell's system for controlling when genes are active," says Ogino, the paper's first author. "One of the signs of this deficiency, it was proposed, is hypomethylation of LINE-1. We wanted to find whether a family history of colorectal cancer creates a higher risk of such hypomethylation."

Fuchs is the paper's senior author.

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