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.
In contrast to a small, previous study, which suggested that LINE-1 hypomethylated colorectal cancers cluster in certain families, the new study took a large-scale "prospective" approach to gain more definitive insights. Investigators used data from the Nurses' Health Study and the Health Professionals Follow-up Study -- which follow the health of tens of thousands of people for decades -- to see if participants who had a family history of colorectal cancer tended to develop colorectal cancer with low-level methylation of LINE-1.
"We found that, compared to individuals without a family history of colorectal cancer, people who had first-degree relatives affected with the disease indeed had a higher risk of developing colorectal cancer with hypomethylated LINE-1," Ogino says. "Because this variety of colorectal cancer can quickly become dangerous, testing colorectal cancer patients for tumor LINE-1 hypomethylation may offer a valuable way of identifying those in greatest need of aggressive treatment. Such testing could also help identify patients whose relatives may be at increased risk for the aggressive form of the disease. Further study is needed to determine how this type of testing can be used in a clinical setting."
In addition to Ogino and Fuchs, the paper's co-authors are Reiko Nishihara, PhD, Paul Lochhead, MBChB, MRCP, Yu Imamura, MD, PhD, Aya Kuchiba, PhD, Teppei Morikawa, MD, PhD, Mai Yamauchi, PhD, Xiaoyun Liao, MD, PhD, Zhi Rong Qian, MD, PhD, Ruifang Sun, MB, Kaori Sato, MS, and Jeffrey Meyerhardt, MD, MPH, of Dana-Farber; Molin Wang, PhD, Donna Spiegelman, ScD, Eva S. Schernhammer, MD, DrPH, and Edward Giovannucci, MD, ScD, of the Harvard School of Public Health and BWH; Andrew T. Chan, MD, MPH, of BWH and Massachusetts General Hospital; and Gregory J. Kirkner, MPH, of BWH.
The study was funded in part by the National Institutes of Health (P01 CA87969, P01 CA55075, P50 CA127003, R01 CA151993, and R01 CA137178), the Bennett Family Fund for Targeted Therapies Research, and the National Colorectal Cancer Research Alliance.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center, and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top-ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter: @dana-farber or Facebook: facebook.com/danafarbercancerinstitute.
Bill Schaller | EurekAlert!
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy