The Age of Surveillance

Q. The science of genetics and DNA testing has traditionally focused on medical applications, expanding from the realm of testing for simple genetic conditions to the much more complex diseases such as breast cancer and diabetes. Is DNA testing being used in the dental office?

A. Yes, DNA testing in the oral cavity is currently in limited use in the dental practice but I think the potential exists for much broader use. Many different possible applications are being studied relative to human genetics and microbial involvement.

DNA TESTING IN PERIODONTAL DISEASES

Q. What are the current uses of DNA testing in the dental office today?

A. DNA testing in the oral cavity is now used in the testing of genes that control the production of interleukin-1 (IL-1). This is an inflammatory cytokine that stimulates bone loss and we think it’s very important in the loss of bone associated with periodontitis. The genetic test is designed to find those patients at risk for accelerated bone loss.

In periodontitis, the amount of bone loss is due to a myriad of factors. Some are genetic; some are local, such as smoking; and some are bacterial. Susceptibility is definitely an issue. Some people may have the same bacteria as others but they don’t develop periodontitis. The test uses a genetic sample from a mucosal scraping, collecting DNA from the harvested epithelial cells to determine whether or not the person falls in the high risk category for the production of IL-1.

Q. Once it is known that a patient falls into this category of high risk, what does this mean for his or her treatment?

A. Those patients at high risk would receive more aggressive treatment. For a patient without this particular risk factor, a regular 6-month professional maintenance appointment may be fine. A patient with this risk factor may need a 3-month follow-up with the administration of antibiotics at defined periods.

Q. Tell us about DNA testing of periodontal pathogens.

A DNA testing of periodontal pathogens is still in its infancy. The methods, however, are both sensitive and specific. We know and can measure the bacteria that are most likely causing the disease condition (the so-called “red complex” bacteria P. gingivalis, T. forsythia, and T. denticola). We know that levels of these bacteria are significantly higher at diseased sites. We know that both systemic and locally-delivered antibiotic therapy can lower the levels of these bacteria and reduce attachment loss for relatively long periods of time. Hence, it is logical that if we treat to maintain low levels of these bacteria, patients should benefit. Convincing demonstration of this last point, however, requires time and longitudinal monitoring.

Q. With DNA testing of the host (patient) and the actual periodontal pathogens, do we have a comprehensive view of patients’ susceptibility to periodontitis?

A. DNA testing of the host to determine susceptibility to periodontitis is also in its infancy. In this case, we are much less confident in our ability to identify all critical areas of genetic control. While we have excellent measures of some genetic factors (such as the genes that control expression of IL-1) factors such as prostaglandin E2, interferon, matrix metalloproteinase enzymes, and a host of other inflammatory pathways that could be significant in connective tissue loss related to periodontal diseases are not well understood. Deciphering the genetic code that spells periodontal disease susceptibility is still in the future. At this point in risk assessment, we are largely dependent on the philosophically frustrating criterion of recognizing susceptibility from past periodontal damage. We can measure periodontal pathogens but a comprehensive view of patient susceptibility continues to elude us.

Q. Will this information help dentists and dental hygienists in treatment planning for patients who demonstrate that they are susceptible to disease?

A. It is an irresolvable predicament of treatment that we must make decisions based on inadequate information. Every piece we have helps but we never have it all. If the patient has diabetes, we can guess that he or she is susceptible to periodontal breakdown. If genetic analysis indicates a proclivity for augmented production of inflammatory mediators, we can guess the patient is susceptible. If the pathogenic bacterial levels are high, we know that etiologic factors are present in abundance. Based on this evidence, a better treatment plan can be made than if the only information available was a charting of probing depths.

Q. How is it determined who should receive DNA testing for interleukin-1?

A. Most periodontal diseases are slow moving. The pre-existence of periodontitis would be a reasonable stimulus for determining if the person falls into the high risk category. The goal is to identify patients who are significantly at risk so a more aggressive therapy can be focused on their condition.

Q. How does DNA testing work exactly?

A. These tests are called single nucleotide polymorphism analyses. A particular area of the DNA is tested to see what nucleic acid is present. This defines the gene category to which the patient belongs and, hence, his or her susceptibility. It is a straight-forward laboratory test.

ORAL CANCER AND DNA TESTING

Q. Is there a possible use for DNA testing in oral cancer diagnosis?

A. Yes, oral cancer diagnosis is an area where I see the use of DNA testing in the oral cavity expanding. Research has found some very interesting positive relationships between oral cancer and oral microbes.1 The issue of oral cancer is a significant concern in clinical practice, although the incidence of oral cancer is very low in terms of the overall percentage of the population. The problem is that when patients are diagnosed with oral cancer it is usually fatal because it’s too late for effective treatment. Other cancer survival rates have greatly improved in the past few decades while oral cancer’s 59% 5-year survival rate has remained unchanged.2

Q. How would DNA testing work in the context of oral cancer?

A. The idea is that the presence of a certain type of microbiota in the oral cavity would be indicative of a cancerous lesion and, therefore, would presumably be an indicator of a need for early intervention. The desired outcome is that the testing could note the transition from what is considered a benign leukoplakia into a cancerous lesion. If the research proves that this is possible, then the goal would be to get the cost low enough where DNA testing in the oral cavity for oral cancer could be a routine screening at every dental appointment.

Q. In the future, if a patient takes a DNA test in the dental office and it shows that he or she has the bacteria related to the development of oral cancer, what happens then?

A. Patients who are identified as having the specific bacteria should be referred to a dentist or physician who specializes in the treatment of oral cancer. This brings up the topic of how oral cancer should be treated at an early stage. Some very interesting technologies are in the pipeline that may change the way we address early diagnosed cases of oral cancer.

One of our investigators has developed the concept that early oral cancer could be eliminated by feeding the patient a compound that increases light absorption in the cancer cells and then shining a light on these cells. This is called phototherapy, which may be able to eradicate leukoplakia before it becomes cancer. The broad arena of oral cancer needs significantly more research before we can be confident in making recommendations to practicing clinicians but the potential is clearly on the horizon.

THE NEW FRONTIER—OBESITY

Q. What other possible applications are in the future for DNA testing in the oral cavity?

A. In the next 6 months, a paper I have written will be published in the Journal of Dental Research on the hypothesis that obesity could be due to the existence of certain bacteria in the oral cavity. At this time, this is only a theory, but if true, the consequences could be dramatic.

Q. If the hypothesis is sound, does this mean that obesity could be treated by killing these specific bacteria in the oral cavity?

A. Yes, in other words, if the organisms causing obesity are targeted then we would be able to reverse obesity. I did a study where I compared the saliva samples of 300 women who were obese to saliva samples of women who were not obese. I found that I could identify essentially 98 percent of the obese women based on their salivary bacteria.

The hypothesis suggests that there is something in the saliva that could be increasing a person’s appetite, metabolic efficiency, or hormonally-induced lipogenesis by a small amount. All that is needed to cause obesity is a 5 percent increase in caloric intake. In other words, a 5 percent increase in calories consumed over 1 year would cause about a 10-pound weight gain, thus a 50-pound weight gain in 5 years. Most likely, many people have these bacteria but some are able to control their weight with exercise and dieting. This complicates research in this area, because not only do the bacteria need to be considered, but so does the caloric intake and exercise level of the subjects.

Another factor of interest is that, in animals, this “obesity infection” affects the assimilation of calories. It has been demonstrated that in a comparison of germ-free animals and animals that are infected, the germ-free animals are more efficient in assimilating calories. If you give an infected animal 100 calories, it will assimilate 90 calories; the germ-free animal will only assimilate 80 calories. If you infect the germ-free animal then it also begins to assimilate 90 calories. This discrepancy can mean the difference between obesity and nonobesity.

ADDITIONAL DENTAL APPLICATIONS

Q. What dental applications for DNA testing are in the future?

A. At some point we may be able to diagnose any type of disease from the oral cavity. The National Institute of Dental and Craniofacial Research is supporting the research that David Wong, DMD, DMSc, is conducting at the University of California, Los Angeles, on determining the total protein profile of saliva. He is investigating the idea that if you know all of the proteins that are contained in saliva you will be able to identify disease in humans.3 This hasn’t yet occurred but it could easily appear within years. Great potential exists for the diagnosis of all sorts of conditions from the oral cavity. The oral cavity is perfect for this type of diagnostic testing because it’s so easy to procure a sample.

Q. Will the dental office be the best place for this larger application of DNA testing in the oral cavity for the diagnosis of all types of diseases, not just those related to oral health?

A. I believe so, I think this science could create the possibility of an enormous screening program. And I am not alone. Dr. Wong’s idea is that there will be a simple handheld device into which the clinician will put the saliva sample and then the device will output that the patient has such-and-such a probability of cancer, diabetes, etc. It sounds futuristic but it’s truly plausible. The dental office may become the center of health surveillance—not just the diagnosis of disease.

Q. Do you think patients will want to know what their risks are for serious diseases?

A. I have discovered in my many years of research that patients really want to believe that they’re healthy. It’s a matter of point of view. If the point of view is that you’re trying to keep people healthy, they will be right behind you. Most people do not want to be diagnosed as being “diseased.” The issue is health surveillance and this is the selling point—keeping healthy people healthy.

REFERENCES

1. Mager DL, Haffajee AD, Devlin PM, Norris CM, Posner MR, Goodson JM. The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med. 2005;3:27.
2. Neville BW, Day TA. Oral cancer and precancerous lesions. CA Cancer J Clin. 2002; 52: 195-215.
3. Wong DT. Salivary diagnostics powered by nanotechnologies, proteomics and genomics. J Am Dent Assoc. 2006;137:313-321

From Dimensions of Dental Hygiene. April 2009; 7(4): 16-18.