|Year : 2017 | Volume
| Issue : 1 | Page : 3-6
Personalized medicine in dentistry
Pushpa S Pudakalkatti, Abhinav Subhashchandra Baheti, Sanjeevini A Hattarki, Soumya S Kambali
Department of Periodontology, Maratha Mandal's Nathajirao G Halgekar Institute of Dental Science's and Research Center, Belgaum, Karnataka, India
|Date of Web Publication||14-Jun-2017|
Abhinav Subhashchandra Baheti
Dwarka Maternity Home, Juna Press, Shevgaon, Ahmednagar - 414 502, Maharashtra
Source of Support: None, Conflict of Interest: None
Personalized medicine is a branch of medicine that proposes customization of healthcare in which decisions and treatment are tailored according to individual patient needs. The field of personalized medicine relies on genetic information, proteomic information and clinical patient characteristics to individualize treatment. With advances in genetics, proteomics, pharmacogenetics and knowledgeable patient population, the opportunity exists to deliver never before levels of personalized care. Although general dentists may consider personalized medicine a concept for the future, the reality is that its direct application to everyday dentistry is closer than one might think. Use of personalized medicine in dentistry, especially in periodontology is progressing rapidly, and dentist should consider this approach while treating patients. Google and PubMed search was done to select articles for present review. Total 17 articles were used to compile information.
Keywords: Genetics, personalized medicine, proteomics
|How to cite this article:|
Pudakalkatti PS, Baheti AS, Hattarki SA, Kambali SS. Personalized medicine in dentistry. J Orofac Sci 2017;9:3-6
|How to cite this URL:|
Pudakalkatti PS, Baheti AS, Hattarki SA, Kambali SS. Personalized medicine in dentistry. J Orofac Sci [serial online] 2017 [cited 2019 Apr 25];9:3-6. Available from: http://www.jofs.in/text.asp?2017/9/1/3/164307
| Introduction|| |
Most of the oral diseases arise from a complex interaction of genetic, biological, behavioral, environmental and various other factors. Because of differential expression and interaction of these factors, individuals differ in their susceptibility and expression of disease.
Personalized medicine is a medical model that involves the customization of healthcare with medical decisions, practices, and/or products being tailored to the individual patient need. Dentists and physicians have long recognized the variation between and among the patients and have provided customized care based on many components that shape individual health.
For collecting information for review, Google and PubMed search were done to select articles. Totally 17 articles were used to compile information.
| How Does it Work?|| |
Though medicine has always been personal to each patient, personalized medicine uses new molecular tools, some kind of technology or discovery, to facilitate highly precise health care based on individual's unique characteristics enabling a level of personalization not previously possible.
In last two decades, there have been many advances in genetics, proteomics, metabolomics, molecular biology and molecular medicine. Personalized medicine uses these advances along with clinical profile and other relevant data to customize the health care services. Personalized medicine is sometimes also labeled as stratified medicine, as patients are stratified based on available information, and then therapy is customized according to characteristics of each stratum. To discriminate from stratified medicine, personalized medicine is more about the individual rather than strata.
In addition, such methods can also be used to assess patient's risk for disease and tailor individual preventive care. It can be done by answering questions like, what is person's risk to develop the disease, what level of care do person needs and what are the chances of success of treatment.
The use of genetic information has played a major role in certain aspects of personalized medicine, and even the term was first coined in the context of genetics but now it is broadened to encompass all sorts of personalization measures.
Genes have a role in normal human development and physiology, and genetic mutation may lead to disease. A common example of genetic mutation is single nucleotide polymorphism (SNP), in which there occurs variation in single nucleotide that may lead to a change in expression of gene. It has been shown that SNP might lead to an increased risk to develop particular disease. Use of genetic tests helps in assessment of risk and even customizing the therapy.
Historically, the pharmaceutical industry has developed medications based on empiric observations and more recently on the basis of known disease mechanisms. For example, antihypertensives have been designed to act on certain pathways involved in hypertension (such as renal salt and water absorption, vascular contractility and/or cardiac output).
Different individuals may have different metabolic pathways, and therefore they respond differently and experience different range and intensity of side-effects to a similar concentration of the same drug. Categorizing individuals by different biological pathways that may produce a different response to the same drug may help in personalizing the care.
Pharmacogenetics examines the impact of genetic variation on the response to therapeutic intervention. This approach is aimed at tailoring drug therapy at a dosage that is most appropriate for an individual patient, with the maximum benefits and minimum side-effects.
Proteomics is comprehensive analysis and characterization of all of the proteins and protein isoforms encoded by the human genome. Even though, the DNA genome is the information archive, it is the proteins that are responsible for functional aspects of the cell like cell movement, cell death.
| Applications in Dentistry|| |
Risk factors like smoking, diabetes, and certain genetic variations are associated with more severe periodontal disease. However in spite of this observation, it is usually assumed that all adults are at equal risk, and similar type of preventive and interceptive care is provided. Because of which, individuals who are at higher risk for developing the disease are inadequately treated, and a individuals who are at lower risk to develop the disease are getting over-treated. Because of missed opportunities to prevent disease in high-risk individuals and unnecessary services rendered in low-risk individuals, health care costs in many countries appear unsustainable.
William Giannobile utilized personalized medicine approach in his study, in which he evaluated tooth loss, which is one of the terminal outcome of untreated periodontal disease in 5117 periodontitis patients, over a period of 16-year. Patients were stratified based on three risk factors, which were smoking, diabetes and interleukin-1 (IL-1) positive genotype. If patients had one or more of these risk factors, the investigators classified them as being at high-risk of periodontitis, and at low risk if they had none of the three risk factors. Authors found that, in low-risk patients, tooth loss was not impacted based on whether the patient visited the dentist once or twice annually. In high-risk patients, two preventive visits compared to one visit per year significantly reduced the number of patients who had tooth loss events. Hence, authors concluded that clinicians should individualize their approach to preventive care based on initial risk assessment and by using personalized preventive care, resources can be put toward the individuals who are at higher risk for disease.
Interleukin-1 is the pro-inflammatory cytokine and presence of IL-1 positive gene is associated with increased inflammatory response. Patients who are genetically positive for IL-1 gene show higher incidence and increased severity of periodontal disease. So, the presence of IL-1 positive gene is considered as a risk factor for periodontitis.
Interleukin-1 genetic test involves the collection of cheek swab for assessment of IL-1 gene. Dentists should consider administering this test as a part of a comprehensive periodontal evaluation. This is especially important for patients who have other risk factors for periodontal disease. This test is available under the trade name of PerioPredict and marketed by IL genetics. At present, this is the only genetic susceptibility test used for periodontal diseases.
Management of dental caries
Prevention strategies include development of small molecules aimed at blocking or weakening enzymes that enable bacteria associated with caries to form a biofilm or attach to the tooth surface.
Dental caries is one of the most common dental problems. Environmental factors, behavioral factors, dietary behaviors, bacterial flora, fluoride intake, oral hygiene, salivary composition, morphological features of the tooth and genetic factors are associated with the occurrence of dental caries in an individual. Wang et al. showed that both shared and unique risk factors may affect dental caries of primary dentition and permanent dentition. Furthermore, genes differentially affect cariogenesis across different surfaces of the permanent dentition.
Assessing a patient's risk of developing caries is a vital component of caries management. Hence, different risk factors associated with dental caries can be used to stratify the patients and customize the therapy. A caries risk assessment should also consider factors that may challenge the patient's ability to maintain good oral hygiene such as crowded dentition, deep fissures, wide open restorative margins and placement of oral appliances.
Discovery of a disease-causing mutation in a family can inform “at-risk” individuals as to whether they are at higher risk for cancer and may prompt individualized prophylactic therapy.
Traditional cancer management has focused on customizing care based on tumor stage, subtype, and histology. Data available from genomic studies allow for more refined tumor classification based on signaling pathways that can be targeted more precisely. Molecular techniques are helping to predict, which lesions are likely to undergo malignant conversion through a better understanding of wide range of proteins and transcription factors that participate in the epithelial-to-mesenchymal transition in squamous cell carcinoma. Personalized care help to better define the prognosis in these patients and to suggest treatment options that are most likely to succeed.
Cancer management by rational drug design
Molecularly targeted therapies have been developed and are being tested for use in head and neck squamous cell carcinoma. An example is tyrosine kinase inhibitor such as imatinib, which have been developed to treat chronic myeloid leukemia. The drug specifically inhibits the Ableson tyrosine kinase protein, hyperproduction of which is strongly correlated with disease. This is thus a prime example of “rational drug design” based on knowledge of disease pathophysiology.
Prevention of recurrence
Minimal residual disease tests are used to quantify residual cancer by detection of tumor markers. It helps in detection of recurrence before even physical signs and symptoms return. Several approaches based on protein expression and nucleic acid analysis show promise toward more accurate prediction of patients at risk for local oral cancer recurrence.
| Challenges|| |
In many ways, improvements are needed to validate routine and effective use of personalized medicine in oral health care. One of the challenges in the implementation of personalized medicine is scientific and technological gap, for example, lack of definitive linkage between biomarkers and genotype.
Personalized medicine approach must have strong clinical utility, means stratification of information must be actionable and should lead to clinical benefit. In addition to the patient, benefits must accrue to other stakeholders such as drug and diagnostics developers, payers (government or private companies) and healthcare providers. A critical element of success of personalized dentistry is public awareness and acceptance of the benefits and risks associated with personal genome sequencing.
| Conclusion|| |
Personalized medicine is not only associated with improvement in treatment but also very useful in preventive care. Personalized medicine has great utilization in diseases like periodontitis, rampant caries, cancers, which have uncertain treatment outcomes. Direct application of personalized medicine to routine dentistry is closer than one might think.
| Future Perspective|| |
At present only IL-1 genetic test is available but there are at least a dozen of genes, which are associated with periodontal disease. So, search for additional genetic markers of periodontal disease and their clinical utilization to personalize the care are essential.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Garcia I, Kuska R, Somerman MJ. Expanding the foundation for personalized medicine: Implications and challenges for dentistry. J Dent Res 2013;92:3S-10.
Fackler JL, McGuire AL. Paving the way to personalized genomic medicine: Steps to successful implementation. Curr Pharmacogenomics Person Med 2009;7:125.
Kornman KS, Duff GW. Personalized medicine: Will dentistry ride the wave or watch from the beach? J Dent Res 2012;91:8S-11.
Shastry BS. Pharmacogenetics and the concept of individualized medicine. Pharmacogenomics J 2006;6:16-21.
Ozdemir V, Williams-Jones B, Glatt SJ, Tsuang MT, Lohr JB, Reist C. Shifting emphasis from pharmacogenomics to theragnostics. Nat Biotechnol 2006;24:942-6.
Van Dyke TE, Sheilesh D. Risk factors for periodontitis. J Int Acad Periodontol 2005;7:3-7.
Keehan SP, Sisko AM, Truffer CJ, Poisal JA, Cuckler GA, Madison AJ, et al.
National health spending projections through 2020: Economic recovery and reform drive faster spending growth. Health Aff (Millwood) 2011;30:1594-605.
Giannobile WV, Braun TM, Caplis AK, Doucette-Stamm L, Duff GW, Kornman KS. Patient stratification for preventive care in dentistry. J Dent Res 2013;92:694-701.
Liu C, Worthington RJ, Melander C, Wu H. A new small molecule specifically inhibits the cariogenic bacterium Streptococcus mutans
in multispecies biofilms. Antimicrob Agents Chemother 2011;55:2679-87.
Hunter PB. Risk factors in dental caries. Int Dent J 1988;38:211-7.
Wang X, Shaffer JR, Weyant RJ, Cuenco KT, DeSensi RS, Crout R, et al.
Genes and their effects on dental caries may differ between primary and permanent dentitions. Caries Res 2010;44:277-84.
Zeng Z, Shaffer JR, Wang X, Feingold E, Weeks DE, Lee M, et al.
Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition. J Dent Res 2013;92:432-7.
Fontana M, Zero DT. Assessing patients' caries risk. J Am Dent Assoc 2006;137:1231-9.
Scanlon CS, Van Tubergen EA, Inglehart RC, D'Silva NJ. Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma. J Dent Res 2013;92:114-21.
van't Veer LJ, Bernards R. Enabling personalized cancer medicine through analysis of gene-expression patterns. Nature 2008;452:564-70.
Saglio G, Morotti A, Mattioli G, Messa E, Giugliano E, Volpe G, et al.
Rational approaches to the design of therapeutics targeting molecular markers: The case of chronic myelogenous leukemia. Ann N
Y Acad Sci 2004;1028:423-31.
Braakhuis BJ, Bloemena E, Leemans CR, Brakenhoff RH. Molecular analysis of surgical margins in head and neck cancer: More than a marginal issue. Oral Oncol 2010;46:485-91.