The role of genetics in our health

Dr. Ana Patiño, researcher at Cima and Director of the Genomic Medicine Unit at the University of Navarra Clinic, explains how health habits and lifestyles can affect gene expression. She addresses the role of genetics in the development of pediatric tumors and advances in personalized therapies. She also highlights the future of personalized medicine and how it will transform the treatment of diseases.

Dr. Ana Patiño, researcher at Cima and Director of the Genomic Medicine Unit at the University of Navarra Clinic.

We know that genetics plays a fundamental role in our identity and health. How do genes influence who we are?

Ana Patiño (AP): Genes are like the instruction manual for a very large and complex construction set that is our identity, health, disease, appearance, and risks. The genes we inherit and pass on to our children may or may not be expressed, and therefore their effects may or may not manifest themselves, and different health habits and lifestyles can affect how genes are expressed, or if they are expressed, or when. It is as if we had all been given the same genetic book, or a very similar one, but, as when we read a real book, the result of reading it will be very different for different people.  

To what extent do our genes determine our destiny in terms of health? Is there any scope for changing what is written in our DNA?

(AP): It depends on many things: the function of the gene, the pathway in which it participates, the type of inheritance, and a term called “penetrance,” which is like the “strength” of the gene on the phenotype. It could be the probability of having a certain genetic alteration manifesting at a certain age. It is expressed as a percentage and gives an idea of the probability of having the clinical condition indicated by the gene. But it is true that part of our health and disease, or our appearance, is greatly influenced by genetics, while another part can be modified, partly at will and partly by life itself, regardless of our desires.

Do environmental factors have any effect on mutations? Can they trigger or prevent diseases? And can we do anything to prevent this?

(AP): Again, it depends on how high the penetrance is. Sometimes it is very difficult to modify the expression of a gene; however, we all understand that good lifestyle habits are aimed at maintaining or restoring health or conditioning or reducing the effects that the gene has on us. It is important to understand that there is a great deal about the function of genes that we do not currently know; in fact, we only have a “somewhat clear” picture of 2-3% of our total DNA. This is a developing science! Another important concept is multigenic or polygenic inheritance (several or many genes playing a role in the same aspect of health) or multifactorial inheritance (genes functioning in one or more different environmental scenarios). The much-mentioned “exposome” refers to all external exposures together with each individual's genome.

In the case of pediatric solid tumors, what role does genetics play in their development?

(AP): Well, it varies greatly depending on the type of tumor. All tumors, in children and adults, are genetic diseases, but only a minority of them are also hereditary diseases. In many cases, we know the alterations that cause the tumor to develop, while in others it is much more heterogeneous and tumors have a genetic pattern that is almost unique to each disease... the scenarios are very different. It is true that it is essential to identify children with hereditary tumors, because the scenario goes from being just the child to being the family, and because surveillance, monitoring, and treatment measures can be implemented to reduce their risks and improve their health.

Is genetic information being used to research and develop more effective therapies for pediatric solid tumors? What advances have been made in this field?

(AP): Genetic alterations often act like buttonholes that open up in tumor cells, through which we can insert therapeutic “buttons,” so that only the cells, tumors, and patients that have those buttonholes will benefit from these personalized treatments. Other times, the alterations are like “Velcro,” in which genetic mutations cause tumor cells to stick to or be attracted to immune system cells, which is a very good idea for treating cancer: immunotherapy. In fact, if we could get the patient's immune system to recognize cancer as the genetically different monster that it is, much of the problem would be solved. In our group, for example, we use viruses that, when injected into the tumor, play a dual role: they directly kill tumor cells and, in addition, because they are a viral infection, they attract lymphocytes that will result in an antitumor immune response.

What role will genetics and personalized medicine play in the treatment of diseases in the future?

(AP):

In my opinion, it will be a radical change. To begin with, in many diseases whose genetic basis is known, it will be possible to use the transfer of a “normal” gene through gene therapy, or to correct the damaged gene through gene editing mechanisms. In addition, there will be many cancer therapies or drugs based directly on the genetics of the tumor, which is already being done with CAR-T therapies, in which modified lymphocytes are used to target markers that are expressed only or preferentially in the tumor.

Clinical trials in cancer and other diseases already select patients based on markers that are genetic markers, and it should not be forgotten that, according to the technical data sheet, many drugs that are currently prescribed to us should be given, not given, or have their dose adjusted in specific patients, based on their genetics. This is pharmacogenetics: giving the right drug to the right patient at the right dose based on their genetic makeup.