[LUM#7] Predicting for better healing

[LUM Magazine] - Published on February 13, 2018 in Science-Society

Individualized medicine that identifies a person's specific risks in order to better prevent and treat disease: these are the promises of predictive and personalized medicine. A rapidly growing field, it opens up new horizons for patients, but also raises many questions...

Why do some people enjoy good health throughout their lives, while others, sometimes from a young age, face the ravages of illness? Regardless of lifestyle, which of course influences our health, we are not all equal when it comes to disease. The reason for this is genetics. A small mutation in our DNA can be responsible for the onset of certain diseases. There is no need to wait for the first symptoms to appear to find out for sure: "Thanks to genetic screening, we can now identify individuals with a particular predisposition or risk," explains Pascal Pujol,anoncogeneticist at Montpellier University Hospital. This is the principle behind predictive and personalized medicine.

Major medical breakthrough

This approach has revolutionized the treatment of certain cancers, such as those caused by mutations in the BRCA 1 and 2 genes. Women who carry these mutated genes have a much higher than average risk of developing cancer, with a 70% probability of breast cancer and a 30% probability of ovarian cancer (Genome-wide association study in BRCA1 mutation carriers identifies new loci associated with breast and ovarian cancer risk, in Plos Genetics, 2013). "When genetic screening reveals these mutations, these patients are offered appropriate follow-up: an MRI scan once a year and surgery between the ages of 40 and 50 to remove the ovaries. Thanks to this protocol, we estimate that we are saving the life of one in four women, which is a major medical breakthrough!" enthuses Pascal Pujol.

Recently, these women have also been able to benefit from specific treatment that targets the genetic mutation. "Predictive medicine thus improves the effectiveness of treatment. We are moving from a screening value to a therapeutic value, which is a real paradigm shift," explains the president of the French Society for Predictive and Personalized Medicine (SFMPP). Already, 25,000 patients have been identified, but the mutation is actually much more common. "We only offer genetic screening to those with a family history of cancer," says Pascal Pujol,"even though in half of all cases, cancer occurs without any family history." (Genesis: a French national resource for studying the missing heritability of breast cancer, in Cancer BMC, 2016). The solution? Extend genetic screening to all women with metastatic breast cancer (Referral for genetic counseling and testing in BRCA1/2 and Lynch syndromes, in Journal of Clinical Oncology, 2013).

When you find what you weren't looking for

While genome sequencing is becoming increasingly popular, it also raises many questions, particularly regarding secondary discoveries. "In 2 to 4% of cases, genetic analyses reveal an abnormality that is unrelated to the one being sought, but which could have serious consequences," explains Pascal Pujol. What should be done with this information? What should be said—or not said—to the patient? "At present, there are simply no regulations," laments the specialist. In half of all cases, the laboratory does not inform the doctor of this discovery. And when they are informed, only one in two practitioners chooses to share this information with the patient. "We can't turn a blind eye. If there are vital issues at stake for the patient, why sweep them under the rug?" asks Pascal Pujol (Role of the general practitioner in the care of BRCA1 and BRCA2 mutation carriers: perspectives of the general practitioner and the patient, in Molecular Genetics and Genomic Medicine, 2018) .

The specialist was confronted with the case of a 15-year-old girl who had undergone genetic testing to investigate intellectual disability. Along with the anomaly responsible for her developmental delay, the analysis revealed a gene predisposing her to colon polyposis. "If nothing is done, this disease degenerates into colon cancer before the age of 40 in 100% of cases," explains Pascal Pujol, who in this case chose to warn the family.

Case by case

For oncogeneticists, the course of action must always be tailored to each individual case, systematically seeking the patient's opinion via specific informed consent. And taking into account the possibility of action: "we differentiate between actionable diseases, those where something can be done, and those that are non-actionable." The goal is to avoid unnecessarily worrying patients, but also to avoid letting them become seriously ill when they could have been treated.

For the president of the SFMPP, it is becoming essential to develop the legislative framework, while considering ethical issues. "If the medical community does not take ownership of this, private companies will take control of predictive medicine, which will then be beyond any control," worries Pascal Pujol. Some companies are already offering a wide range of tests, carried out without any medical supervision. "Patients thus find themselves in possession of information about their genome, sometimes meaningless, and they don't know what to do with it. The public debate that will be launched in 2018 and the revision of the bioethics law in 2019 will be an excellent opportunity to reflect on these issues from a medical and societal perspective."

Keywords: LUM#7, LUM Magazine, Medicine, Research, Health