Apr 19 2005
In future scientists say, a test as simple as spitting into a collection tube or cup might be a screening test for breast cancer and the early detection of other tumours.
According to new studies by UCLA researchers genetic "biomarkers" isolated in saliva predicted oral squamous cell carcinoma in about nine out of 10 cases and could be equally precise in similar predictive powers for head and neck cancers.
David T. Wong, professor and associate dean of research at the UCLA School of Dentistry and the Jonsson Comprehensive Cancer Centre, the study's senior investigator, says the study, which was based on a risk model , indicates that biomarkers found in saliva, called salivary transcriptomes, can be exploited for robust, high-throughput and reproducible tools for early disease detection.
Scientists have long been searching for quick and easy screening tools that could be done in a doctor's office and the search for such tests which could harvest saliva and other bodily fluids for molecules that detect early cancers has been accelerated with the advance of several emerging technologies including improved methods to identify, collect, preserve and amplify genetic material and proteins.
The UCLA team found they could isolate messenger RNA from saliva and blood sera that might have diagnostic value for detecting early cancer. In the cell, messenger RNA or mRNA carries a copy of the genetic code or DNA, housed in the cell's nucleus, to other parts of the cell for protein manufacture. The process by which genes are copied to mRNA, via an enzyme called RNA polymerase, is called transcription and the products are called transcripts.
Saliva and blood was collected from 32 patients with primary oral squamous cell carcinoma and 40 breast cancer patients, and matched with saliva and blood from otherwise normal subjects. New techniques were developed to halt RNA degradation so the scientists could recover as much mRNA as possible for their samples. In all, the new techniques allowed the scientists to harvest up to 10,000 types of human mRNA from saliva, setting up a comparison test between cancer patients and the normal subjects based on analysis of their genetic "profiles."
Wong says that both the serum and the saliva exhibited unique genetic profiles. The risk model yielded a predictive power of 95 percent by using only the salivary transcriptome samples and 88 percent by using only serum transcriptome samples for oral squamous cell carcinomas and for oral cancer, salivary transcriptome has a slight edge of that of serum transcriptome analysis.
It is expected that future research will involve a larger sample of cancer patients to refine prediction models and will also include studies involving precancers and other difficult to detect cancers such as ovarian and pancreatic cancers. The study proves the principal but the results will need to be validated in a larger sample size in a blinded manner.
Wong feels one of the biggest hurdles stems from the fact that salivary nucleic acids or protein markers might be influenced by eating, drinking, smoking, diet or oral hygiene, and they aim to provide the optimized and standardized protocol to assure consistent results.
The studies are supported by grants from the U.S. Public Health Service (National Institute of Dental & Craniofacial Research) and the UCLA Jonsson Comprehensive Cancer Centre to David T. Wong.
Also participating in the study were Yang Li, David Elashoff, MyungShin Oh, Stephanie Tsung, and Mai N. Brooks at UCLA.
The study is published in Clinical Cancer Research and was presented at the Annual Meeting of the American Association for Cancer Research.