Embracing Personalized Medicine in Dentistry.

AIM: The aim of this systematic review was to evaluate the number of articles in the area of personalized medicine specific to dentistry.
MATERIALS AND METHODS: Electronic search using three databases was performed using PubMed, Embase, and Scopus search.
RESULTS: Results suggest that there is a definite need for more awareness and research pertaining to this specific area.
CONCLUSION: With this background, the authors have written a comprehensive review on applications of personalized medicine in various branches of dentistry.

INTRODUCTION

Personalized medicine is a progressing area in which physicians use diagnostic tests to identify particular biological markers, often genetic, that aid in describing which medical treatments, as well as technique, will work best for each patient. In today’s science, researchers are rapidly emerging and using diagnostic tests in medical diagnosis based on genomic, proteomics, and metabolomics to enhance and prophesy patient’s reactions to targeted therapy. This area designated as “personalized medicine” conglomerates human genome, information technology, and biotechnology with nanotechnology to provide cure based on specific difference set against population trends.[12]

Also, a budding contingent of scientists, certain clinicians, and a growing number of patients are on the lookout for a more personalized approach to preventing diseases as it is at tailoring treatment once it is there. It may be called personalized medicine, genomic medicine, or precession medicine; it is a method that puts emphasis on the way in which patient disease risks are distinctive and not the same just like other more obvious characteristics. Those diseases risks are based on predilection transcribed in patient’s genomics at birth pooled with patient’s lifestyle and environmental factors.

Personalized medicine now in the age of genomics means we are living in dynamic times. The big question right now is how do we take all this new information we have gathered and use it for the benefit of the patient. Although personalized medicine in the medical field is escalating and becoming more common, in dentistry it is still in infancy and there are not yet enough products in the market that have penetrated the average consciences of the patient.

Exploration and advancement in personalized medicine is a rapidly growing domain, as reviled by numerous medical publications. Most of the available literature stressed on genetic analysis, health information management, biomarker detection, and targeted therapies.[34]

Distinguishing a diseased individual from others with similar clinical presentations forms the basis of precision dentistry and medicine. The principle in treatment involves targeting patient’s precise needs on the source of genetic, biomarker, epigenetic, and socioeconomics. The objective is to reduce errors in diagnosis, develop outcomes, and elude needless side effects. Precision medicine is poised to profoundly transform how clinicians approach health care. This article will explore the foundations of individualized therapy—as well as the challenges and future opportunities for precision health care.

For collecting information for review, Google and PubMed search were performed using keywords such as personalized medicine, to select articles.

Personalized medicine covers key areas such as advances in molecular diagnosis, cost–benefit issues for precision medicine, impact of precision medicine on health care and pharmaceutical industry, and influence on modern concepts in the development of precession medicine based on pharmacogenomics, pharmacogenetics, and pharmacoproteomics.

Opportunity, challenges, and feature of personalized medicine that could be implemented to personalized dentistry are the following:

Directing targeted therapy and reducing trial-and-error procedures

Decreasing adverse drug reactions

Increasing patient willingness to treatment

Reducing high-risk invasive testing procedures

Facilitating to control overall cost of health care

MATERIALS AND METHODS

Protocol

Present systemic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines.

Eligibility criteria, information sources, and search strategy

A literature survey was conducted to identify studies using search engines PubMed, Embase, and SciELO from 2008 to May 2018. The keywords used were personalized medicine, dentistry, periodontics, orthodontics, and oral cancer.

Study selection

Full-text articles published in English language only were included in the analysis. Search was further filtered to include only research articles. Research articles with emphasis on personalized medicine in dentistry were selected.

RESULTS

Results suggest that there is a definite need for more awareness and research pertaining to this specific area.

Why personalizsed medicine for dentistry?

Dentistry may not be the first thing people think of when it comes to personalized medicine, but it ties into what is known as “systemic health.” Dentistry, by its nature, is very personal in its form of delivering treatment. The aim was to customize tailored dental method aimed at identification of different levels of what was previously considered as risk factors for the development of dental problems and then to look at one of the end results of advanced disease conditions such as tooth loss, dental caries, oral cancer, and malocclusion.

Benefits of pharmacogenomics in dentistry

Drug dosage: Pharmacogenomics will replace traditional methods of drug dosage based on age and weight to a dosage determined by efficacy and metabolism of the drug in the body.

Early screening for disease: It provides knowledge of each patient’s genetic information, which in turn allows individuals to make suitable lifestyle and environmental changes at an early age in order to prevent the disease. Similarly, early information about susceptibility to a specific disease will help in careful monitoring and render treatments to capitalize on its therapeutic benefit.[5]

Application/role of personalized medicine in dentistry

Periodontal application

The latest research proposes that by integrating a tailored medicine model into preventive care for periodontitis, general dentists can more efficiently allocate both time and resources to the highest risk patients affected by this disease. The association between oral and systemic disease—i.e., the perio-systemic linkage—is currently sound.[6] Presently, focus on the etiology of periodontitis has shifted from bacterial plaque to host–bacterial interactions and examining the impact of inflammation response on host tissues.[789]

Traditionally, diagnosis for periodontal disease is based on obtaining patient’s history along with traditional clinical assessments.[10] On the basis of this observation, it is usually assumed that patients are at risk, and similar type of preventive and interceptive care was provided. As a result of this, patient who is at greater risk of developing the disease is inadequately treated, and patients who are at lower risk to develop the disease were over treated.

As a result, cost of treatment in different parts of the world was unjustifiable.[11] As scientists carry on to study further with respect to periodontitis and its risk factors, the treatment rendered toward these patients will probably turn into a customized one. The practice of personalized medicine in dentistry, and in specific periodontology, is at present developing beyond theory to a new way for clinicians to approach and provide oral care in their daily practices.

Currently, periodontitis is considered to be a polymicrobial infection. Research has shown that a portion of the clinical variability in periodontal disease could well be clarified through genetic factors. Genes can affect host–bacterial interactions in the periodontal tissues due to elevated levels of proinflammatory cytokines, such as interleukin-1 (IL-1). IL-1 plays a dynamic role in the pathogenesis of periodontitis, by regulating host’s inflammatory response and thereby resulting in bone resorption. As a result, the genes that encrypt IL-1 production in recent times received utmost attention as likely predictors for periodontal disease progression. Therefore, the association between IL-1 genotype and periodontal disease has been investigated by various authors.[1213]

Promising results have been shown with IL-1, which is the pro-inflammatory cytokine, and presence of the IL-1 positive gene is associated with increased inflammatory response. Subjects who are genetically positive for IL-1 gene showed higher incidence and the increased severity of periodontal disease. So, the presence of the IL-1 positive gene is considered as a risk factor for periodontitis.

Authors have reported no significant variants was observed when genome-wide association studies were conducted in patients with chronic periodontitis (CP), but they reported CDKN2BAS variants on chromosome 9 were significantly linked to aggressive periodontitis. Prevention outcomes were evaluated to differentiate CP by stratifying patients into IL-1 gene variants, smoking, and diabetes.[14151617]

At present, this is the only one commercially available genetic susceptibility test used for periodontal diseases, which is traded under the name PerioPridict that evaluates IL 1. In the coming time, further genetic markers can be recognized, which could play a role in identifying periodontitis at an early stage.[1819]

Dental caries

One of the most important public health problems across the world related to oral health is dental Caries. According to World Health Organization statistics, it is estimated that dental caries affects about 60–90% of school-going children and a vast majority of adults and that dental caries is considered as the primary cause for tooth loss globally.[20] The lifelong experience of severe dental caries and periodontal disease will ultimately result in tooth loss, which will in turn greatly affects the quality of people’s life. The cause of dental caries is mainly due bacteria present in the biofilms, which in turn converts sugars into acids that result in demineralization of tooth enamel, dentin.[21]

Various factors can influence dental caries, which are broadly divided into environmental and host factors. Environmental factors such as dietary habits, usage of fluoride, and personal oral care, and host factors such as salivary composition, enamel structure, taste preferences, and immune responses vary among children and may be genetically determined.[22]

Various schoolwork have reported that 40–60% of dental caries susceptibility is genetically determined. They also reported that dental caries is influenced by numerous genomic and loci factors, such as mutation in the single-nucleotide polymorphism of Amel X responsible for normal enamel development, defect in KLK4 gene responsible for enamel maturation, LYZL2 that involves in antibacterial defenses, and AJAP1 that may influence tooth development.[232425] As a result, early detection of these specific genes not only benefits the patient but also the dentist who can render better treatment to the patient with thorough knowledge with respect to its diagnosis and prognosis.[26]

Personalized medicine for oral cancer

Oral cancer is one of the most common malignant lesions of the head and neck. Oral cancer is believed to develop due to a number of molecular inequities that affect strategic genes and signaling pathways. The mechanisms involved in the pathogenesis and development of oral cancer still require extensive research and understanding.[27] Survival rate of patient with oral cancer depends on early detection of this disease entity and use of vigorous screening techniques.[28] This is more likely to be possible if a biomarker-based method is employed for early detection of oral cancer, eventually leading to better treatment outcomes and enhanced survival rate.[29]

Recent developments in the influential omics tools, which include genomics, epigenomics, transcriptomics, proteomics, metabolomics, and lipidomics are initiating novel paths in the direction of biomarker detection for prompt diagnosis of oral cancer. The detection of these biomarkers facilitates in determining and discriminating the behavior of oral cancer in each of the affected patients thus, providing personalized therapies for these patients.[27] In head and neck cancer, the specific antibody response is generated by the body as a part of an anticancer immune reaction against cancer-specific antigens. These specific antibodies can be used for early detection of cancer.[30]

Once the nature of cancer is established in early stage, effective management strategy can be made with options of chemotherapy, radiotherapy, and surgery. The option or combination of options can be tailor-made for each patient based on the sensitivity of cancer cells rather than one common protocol for all patients with head and neck cancer.[28]

Personalized orthodontics

In the field of orthodontics, genetics has its own prominence as its concepts are evolving day by day over the past century period. The knowledge of genetics related to orthodontics is helpful in understanding the etiology of the malocclusion, normal variation between individuals, and prevention of malocclusion to some degree. The comparative influence of genetics and environmental factors in the etiology of malocclusion has been a matter of debate; deliberation and controversy in the orthodontic literature exist for over the decades and always persist as combative subject.[31] But in current times, the advanced genetic research studies are focusing toward genomic basis of craniofacial growth and genetic variants of dentofacial abnormalities. Such genomic-associated research has laid path toward an innovative mode of orthodontics, which is called as personalized orthodontics. Personalized orthodontics is customized to an individual in whom the genomic evidence and clinical data can be utilized and the susceptibility of developing malocclusion(s) can be anticipated, and consequently, treatment plan is implemented in a precise manner.[32] In orthodontics, for instance, mandibular prognathism (Class III) and cleft lip and palate are primarily genetic in origin and also certain number of them are environmental in origin.

Class III malocclusion—mandibular protrusion obvious in Spain Charles royal families, also called as Hapsburg jaw— is considered as a monogenic dominant phenotype, and is also an expression of certain genes that encode specific growth factors (Indian hedgehog homolog, parathyroid-hormone like hormone, insulin-like growth factor-1, vascular endothelial growth factor, harbor genes [chromosomal loci 1p36, 12q23, and 12q13], etc.) accountable for Class III malocclusion.[3334]

Certain genes—transmembrane protein 1 and GAD1—are responsible for occurrence of cleft lip and cleft palate and also certain genetic variants REF IRF6, PVRL1, and MSX1 are involved in the formation of syndromic-associated cleft lip and palate.[3536]

In such conditions (e.g., cleft lip and palate and Class III), near prospect personalized orthodontics may play a vital role by the deployment of individual’s genomic evidence, thereby the risk factors can be anticipated and precise orthodontic care is concentrated.

CONCLUSION

Current proof advocates that we can apply our collective knowledge with regard to precise risk factors comprising the novel concepts of genetics to enable deterrent medical facilities to individuals who certainly require it and improve patient’s oral health.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.