Scientists at the Johns Hopkins Kimmel Cancer Center, Baltimore, have identified chemically altered genes in saliva common only to head and neck cancers, according to a study published in the January 1 issue of Clinical Cancer Research.
Two hundred eleven patients with head and neck cancer and 527 people without cancers of the mouth, larynx or pharynx brushed the inside of their mouths, then rinsed and gargled with a salt solution.
The investigators collected the rinsed saliva and filtered out cells thought to contain one or more of 21 bits of chemically altered genes common only to head and neck cancers. They also collected tumor and blood samples.
The cellular mishaps occur when small molecules called methyl groups clamp on to the DNA ladder structure of a gene. In the grip of too many methyl groups, these genes can incorrectly switch on or off in a process termed "hypermethylation." "Mass-methylation" of particular genes can lead to cancer, the researchers report.
"The challenge is to predict which hypermethylated genes are most specific to cancer," said lead investigator Joseph Califano, MD, an associate professor of otolaryngology—head and neck cancer and oncology. Because every cancer process involves a unique genetic fingerprint, combining several gene signatures for the disease rather than using single ones may identify a larger percentage of patients with cancer.
The researchers noted that of 21 hypermethylated genes, seven were the best predictors of cancer within cell-laden saliva. They tested panels of three to five of these genes on salivary rinses.
One panel correctly identified 66 (42.9 percent) of 154 patients with the disease and accurately ruled out the disease in 203 (81.9 percent) of 248 healthy subjects.
The researchers also used a different set of seven hyper-methylated genes among blood samples. Although the blood test was more accurate than the salivary test in detecting cancer in patients with the disease (34 of 37), there was a trade-off in the number of healthy people it identified (53 of 173).
"Few tests can be perfect 100 percent of the time in identifying both normal and cancerous cells," said Dr. Califano. "Because head and neck cancers are not widespread, it makes more sense to screen those at high risk and to focus on a test’s ability to accurately rule out healthy people."
More studies are needed to refine the test by uncovering additional hypermethylated genes that play a role, as well as to automate the test before multi-institutional clinical trials can begin. One of the first clinical uses for such a test could be to detect recurrence in patients with head and neck cancer.
This study was funded by the Damon Runyon Cancer Research Foundation, the Flight Attendant Medical Research Institute, the National Institute of Dental and Craniofacial Research and the National Cancer Institute.
