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!
ARTORG and Inselspital develop artificial pancreas
26.11.2015 | Universitätsspital Bern
Laboratory study: Scientists from Cologne explore a new approach to prevent newborn epilepsies
24.11.2015 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
Wissenschaftler aus Tübingen und Houston haben zahlreiche neue Zelltypen im Gehirn identifiziert. Im Neocortex von erwachsenen Mäusen führten sie erstmals eine...
Ende der 1980er Jahre erlebte die Erde eine dramatische Klimaveränderung. Sie umfasste die Tiefen der Ozeane ebenso wie die obere Atmosphäre und reichte vom Nord- bis zum Südpol. Ausgelöst durch den Ausbruch des Vulkans El Chichón in Mexico 1982 und verstärkt durch menschliches Handeln folgte daraus die größte Temperaturverschiebung der letzten 1.000 Jahre. Erstmals nachgewiesen hat dies ein internationales Forscherteam um Prof. Philip C. Reid von der Plymouth University und der Sir Alister Hardy Foundation for Ocean Science (UK). Die Ergebnisse wurden kürzlich in der Fachzeitschrift „Global Change Biology“ veröffentlicht.
Abrupte Klimaveränderungen haben oft dramatische Folgen für unseren Planeten. Dennoch sind sie in ihrer Art, ihrem Ausmaß und in ihrer Wirkungsweise meist nur...
Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.
Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...
Fraunhofer ISE demonstriert neue Zell- und Modultechnologien an der Außenfassade eines Laborgebäudes
Das Fraunhofer-Institut für Solare Energiesysteme ISE hat die Außenfassade eines seiner Laborgebäude mit 70 Photovoltaik-Modulen ausgerüstet. Die Module...
The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...
27.11.2015 | Veranstaltungen
27.11.2015 | Veranstaltungen
26.11.2015 | Veranstaltungen
27.11.2015 | Förderungen Preise
27.11.2015 | Unternehmensmeldung
27.11.2015 | Energie und Elektrotechnik