A team led by Johns Hopkins researchers has found that a hereditary colon cancer syndrome, familial adenomatous polyposis (FAP), is associated with abnormally dense blood vessel growth in the skin lining the mouth.
The finding, reported in the June issue of Familial Cancer, could lead to a quick screening test for FAP, which is normally diagnosed with expensive DNA tests and colonoscopies, and sometimes goes unnoticed until cancer develops.
“This higher blood vessel density in the mouth may reflect an abnormal state of cells lining the digestive tract – including the oral cavity – that predisposes people to colorectal cancer and precancerous polyps,” says Francis M. Giardiello, M.D., Johns G. Rangos Sr. Professor of Medicine at Johns Hopkins and director of Hopkins’ Hereditary Colorectal Cancer Program.
People who have even one copy of the mutant gene that causes FAP develop hundreds of precancerous colorectal polyps, also known as adenomas, in their teens. Most have their colons removed after diagnosis to avoid what would otherwise be a near-100 percent risk of colon cancer by middle age.
In 2003, Italian researchers reported that a similar genetic condition, hereditary non-polyposis colorectal cancer (HNPCC), was linked to a greater complexity of blood vessels in the oral mucosa – the skin that lines the mouth. Daniel L. Edelstein, a senior research program coordinator at Johns Hopkins University School of Medicine, says he read the Italian report and brought it to Giardiello’s attention.
Edelstein also contacted Jessica C. Ramella-Roman, an expert on bio-optics systems at The Catholic University of America. “She developed a cameralike device that enabled a direct and relatively automated measurement of this vascular density in the lining of the mouth,” he says.
Using Ramella-Roman’s device and associated image-analysis software, the researchers scanned a two-centimeter-square patch of oral mucosa inside the lower lip of 33 patients with FAP. All 33 were enrolled in the Johns Hopkins Hereditary Colorectal Cancer Registry. The team also scanned a similar tissue sample of 50 control subjects who were matched for age and other variables but had no personal or family history of colorectal cancer or adenoma(s). Each subject was screened to determine the density of visible blood vessels in their lower lip – a measure they called the “oral mucosal vascular density (OMVD).”
“The OMVD measures were significantly higher in FAP patients than in healthy controls,” says Giardiello. “About 90 percent of FAP patients in this sample had OMVD values above a certain threshold, and about 90 percent of controls were below that threshold, so in principle, we could use that threshold for screening purposes.” Differences in the OMVD results were unrelated to age or gender, according to the researchers.
To further investigate the technique’s screening potential, the researchers gave the OMVD test to five of Giardiello’s patients who had multiple polyps but no detectable mutation for FAP or HNPCC on genetic tests. “They might have other, unknown gene mutations predisposing them to polyp formation, or they might have FAP or HNPCC mutations that somehow weren’t picked up in the tests,” said Giardiello.
All five of these patients had OMVD scores above the high-risk threshold. “The results suggest that this high-OMVD condition may be an alternative marker for colon cancer risk, even when we can’t find a gene mutation,” Giardiello says.
Tumors typically promote the spread of new blood vessels in their vicinity to maintain their high growth rates. FAP mutations also boost the production of factors that increase new-vessel growth in the colon and other tissues. That could explain why people with FAP have higher vascular densities in their mouths, says Giardiello.
“While there seems to be a reason why FAP patients have this denser vessel growth, I don’t yet have a plausible explanation for how HNPCC gene mutations could cause this overgrowth,” says Giardiello. “It’s something that we’d like to investigate further.”
The study was supported by The John G. Rangos Sr. Charitable Foundation, and The Clayton Fund.
Other researchers who participated in the study were Ali Basiri of the Catholic University of America; Linda M. Hylind, Katharine Romans, and Jennifer E. Axilbund of Johns Hopkins; and Marcia Cruz-Correa of the University of Puerto Rico.Johns Hopkins Kimmel Cancer Center
Vanessa Wasta | EurekAlert!
Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology
Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
18.10.2017 | Materials Sciences
18.10.2017 | Physics and Astronomy
18.10.2017 | Physics and Astronomy