Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Patients with family history of colorectal cancer may be at risk for aggressive form of the disease

13.12.2012
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.

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!
Further information:
http://www.dfci.harvard.edu

More articles from Health and Medicine:

nachricht New antibody analysis accelerates rational vaccine design
09.08.2018 | Scripps Research Institute

nachricht Distrust of power influences choice of medical procedures
01.08.2018 | Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>