Health and Personalized Medicine

What do we mean by personalized and precision medicine?

Precision medicine is an emerging approach to disease treatment and prevention that considers the variability between people, both genetically and in the individual’s environment and lifestyle. This approach will enable both physicians and researchers to predict more accurately which treatment and prevention strategies for a given disease will work in particular groups of people.

The terms “precision medicine” and “personalized medicine” are commonly used interchangeably, however, they do not mean exactly the same thing. The term “personalized medicine” is an older term that has been replaced by “precision medicine” to prevent it from being misinterpreted to mean that treatments and preventions are developed uniquely for each individual. In precision medicine, the focus is on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors (1).

This new perspective represents a fundamental shift from the “one-size-fits-all” paradigm for clinical treatment, evolving towards novel approaches, such as patient-tailored therapies, with the aim of achieving better outcomes (2). Thus, in the coming years, medicine will progressively shift from being reactive and disease-based to being health-centered. This type of medicine is commonly referred to as P5 medicine, since it is personalized, predictive, preventive, participatory and population-based medicine. This new way of understanding medicine is personalized, because it is based on the genetic, environmental and lifestyle information of each person; predictive, because this personalized information makes it possible to determine the individual risk of suffering certain diseases; preventive, because, based on the prediction of this risk, prophylactic measures (both lifestyle and therapeutic) can be established to reduce it; participatory, because many of the prophylactic interventions require the participation of the patient and a change in the doctor-patient relationship; and population-based, because it offers the possibility of making the system more efficient and thus, with the same resources, managing to serve a larger volume of the population (3). 

In general terms, precision medicine can be divided into three main branches: prevention, diagnosis, and treatment.

• In terms of prevention, we can say that advances in patient screening, based on family history and the identification of genetic variants associated with a higher probability of disease occurrence, have led to significant improvements in prevention for specific at-risk populations (4).
• In terms of diagnosis, precision medicine involves new, more complex diagnostic classifications based on genetic, phenotypic or psychosocial factors, as well as biomarkers, that differentiate subgroups of patients within a given disease. A biomarker, or biological marker, is defined as a characteristic that can be objectively measured and evaluated as an indicator of a normal biological, pathological, or pharmacological response to a therapeutic intervention (5).
• On another note, precision medicine includes the development of new personalized treatments applicable only to specific groups of patients suffering from the same disease, known as pharmacogenetics.

Pharmacogenetics is a part of precision medicine that studies how a person’s genetic makeup influences how he or she responds to drugs. The Food and Drug Administration (FDA) currently includes pharmacogenetic information on the labels of about 200 drugs, consisting of measurable or identifiable genetic information that can be used to individualize the use of drugs (6,7).

Figure 1. Main applications of personalized medicine. Prevention, diagnosis and treatment (8)

The era of “omics” and its importance in precision medicine.

The dissemination of “multi-omics” analyses, together with access to large-scale clinical, behavioral, and environmental information, will make it possible to digitize the state of health or disease of each individual, and to create a global health management system capable of generating real-time knowledge and new opportunities for prevention and therapy at the individual level (9).

Omics sciences can be defined as the part of biology that analyzes the structure and functions of the whole of a given biological function, at different levels, including:

• Genomics: identification of genetic variants associated with the disease, response to treatment or future prognosis of patients.
• Epigenomics: characterization of reversible modifications of DNA or DNA-associated proteins.
• Transcriptomics: study of the RNA resulting from the expression of a cell.
• Proteomics: large-scale study of proteins.
• Metabolomics: study of multiple types of small molecules, such as amino acids, fatty acids, carbohydrates, or other products of cellular metabolic functions.
• Metagenomics: study of a mixture of genetic material extracted from a community of organisms.

Genomics is the most developed of the omics sciences, although the other fields are very promising. In the field of medical research, genomics focuses on the identification of genetic variants associated with disease, response to treatment or the patient’s future prognosis. 

This field makes extensive use of genome-wide association studies (GWAS), a successful approach that has been used to identify thousands of genetic variants associated with complex diseases in multiple human populations. In these studies, millions of genetic markers are analyzed in thousands of individuals, and differences between cases and controls are considered evidence of association. GWAS studies make an invaluable contribution to our understanding of complex phenotypes (10,11).

In the future, it will be essential to combine the knowledge of the different omics sciences, which will make it possible to obtain a global and detailed vision of people from the molecular point of view, thus enabling precision medicine to be carried out. The omics sciences will be key in early diagnosis, in the choice of the best treatment and in the development of new preventive intervention technologies.

Examples of precision medicine applications

• Alzheimer’s disease

Population attributable risk models estimate that up to one-third of AD cases can be prevented by modifying risk factors. The field of AD prevention has largely focused on addressing these factors through universal risk reduction strategies for the general population. However, targeting these strategies to clinical precision medicine, including the use of genetic risk factors, allows for a potentially greater impact on AD risk reduction (12).

Furthermore, it is known that neuroinflammation begins decades before the clinical onset of AD and represents one of the earliest alterations in the entire AD disease process. Large-scale genome-wide association studies (GWAS) point to several genetic variants – including TREML2, CD33, CR1, MS4A, CLU, and EPHA1 – potentially linked to neuroinflammation. Most of these genes are involved in proinflammatory intracellular signaling, cytokine/interleukin/cell turnover, synaptic activity, lipid metabolism, and vesicle trafficking (13).

• PD-L1 in cancer

Cancer is a term that describes diseases in which abnormal cells multiply uncontrollably and invade nearby tissues. It is, rather than a disease, a group of more than 200 diseases that share a series of characteristics that lead to uncontrolled cell growth. It is therefore highly heterogeneous, which makes it essential to select a specific treatment regimen for each patient. In the selection of this treatment, the overall risk to the patient in the absence of treatment, the benefit to the patient derived from the treatment and the possible adverse effects of the treatment for the patient are evaluated (14).

A specific example of a biomarker used for this purpose is the PD-L1 protein, whose biological function is to prevent cells of the immune system from attacking healthy cells. When a cell expresses PD-L1, it is signaling to the immune system that it is a healthy cell and should not be attacked, but sometimes tumor cells can also express PD-L1 and this causes the immune system not to recognize them as tumor cells and fight the tumor.

There are numerous therapeutic options based on “anti-PD-L1”, which neutralize this PD-L1 expression and make the tumor vulnerable to its own immune cells. Therefore, the expression of PD-L1 by the tumor establishes the response to treatment (15).

• Warfarina (pharmacogenetics)

Warfarin is an oral anticoagulant used worldwide to treat and prevent thrombotic disorders. Although it is highly effective, it has a very narrow therapeutic index that makes it difficult to dose correctly.

Genetic variants in the cytochrome P450-2C9 and vitamin K-epoxide reductase complex enzymes, encoded by the CYP2C9 and VKORC1 genes, respectively, along with nongenetic factors, affect the variability of warfarin dosing. Patients with specific variants in one of these two genes may require a lower dose of warfarin compared to patients without these variants.

But, in addition, the combination of genetic variants in both genes (CYP2C9 and VKORC1), together with clinical factors, may put some patients at risk for adverse events such as hemorrhages. Therefore, it is essential to know the genotype of patients for these variants in order to avoid this and other potential adverse effects (16, 17).

Health Testing and Pharmacogenetics at 24Genetics: a first step to Personalized Medicine

At 24Genetics we have preventive Health and Pharmacogenetics, tests, which offer a wealth of scientifically validated information that tells you what parts of your health and well-being you should pay more attention to. It’s an overview of your health, which makes it a great prevention tool and a first step to personalized medicine.

In addition, our Health Plus Pack includes our Nutrigenetics and Ancestry tests, along with the aforementioned Health and Pharmacogenetics tests.