[LUM#7] Prediction for a better cure

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

Predictive and personalized medicine offers the promise of individualized medicine that can identify risks specific to a given person, enabling better prevention and treatment. This fast-growing discipline opens up new horizons for patients, but also raises many questions...

Why do some people enjoy flourishing health throughout their lives, while others face the horrors of illness, sometimes from an early age? Apart from lifestyle, which of course influences our health, we are not all equal when it comes to disease. The cause: genetics. A small mutation in our DNA alone can be responsible for the onset of certain pathologies. We don't have to wait for the first symptoms to know for sure: " thanks to genetic screening, we can now identify a person with a particular predisposition or risk ", explains Pascal Pujol, oncogeneticist at Montpellier University Hospital. This is the principle of predictive and personalized medicine.

A 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 carrying 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 riskin Plos Genetics, 2013). " When genetic screening reveals these mutations, we offer these patients appropriate follow-up: an MRI scan every year and an operation between the ages of 40 and 50 to remove the ovaries. Thanks to this protocol, we estimate that we're saving the lives of one woman in four - a major medical advance! " enthuses Pascal Pujol.

Recently, these women have also been able to benefit from a specific treatment that targets the genetic mutation. " Predictive medicine makes it possible to improve treatment efficacy. We're moving from a screening value to a therapeutic value - it's a real paradigm shift ", explains the President of the French Society for Predictive and Personalized Medicine (SFMPP). Already 25,000 affected patients have been identified, but the mutation is actually much more common. Pascal Pujol explains: " Genetic screening is only offered to those with a family history of cancer , whereas in one out of every two cases, cancer occurs without a family history " (Genesis: a French national resource to study the missing heritability of breast cancerin 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 syndromesin Journal of Clinical Oncology, 2013).

When you find what you weren't looking for

While genome decryption is becoming increasingly popular, it also raises a number of questions, not least that of secondary discoveries. " In 2-4% of cases, genetic analysis reveals an anomaly unrelated to the one we're looking for, but with potentially serious consequences," explains Pascal Pujol. What to do with this information? What should we tell - or not tell - the patient? " For the time being, there are simply no regulations," laments the specialist. In one case out of two, the laboratory does not inform the doctor of the discovery. And when they are informed, only one practitioner in two chooses to inform the patient. " If there are vital issues at stake for the patient, why sweep them under the carpet?" asks Pascal Pujol (The role of the general practitioner in the management of BRCA1 and BRCA2 mutation carriers: perspectives of the general practitioner and the patientin Génétique moléculaire et médecine génomique, 2018).

The specialist was confronted with the case of a 15-year-old girl who had undergone genetic analysis to investigate an intellectual deficiency. Alongside the anomaly responsible for her retardation, the analysis revealed a gene predisposing her to polyposis of the colon. " 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 the oncogeneticist, the course of action must always be adapted to each individual case, systematically seeking the patient's opinion via a specific informed consent form. And by taking into account the possibility of taking action: " we differentiate between diseases that can be acted upon, those where something can be done, and those that cannot ". The aim is not to worry patients unnecessarily, but also not to let them fall seriously ill when they could have been treated.

For the president of the SFMPP, it is becoming essential to develop the legislative framework, while thinking ethically. " If the medical community doesn't get to grips with the issue, private companies will have a stranglehold on predictive medicine, which will escape all control ", worries Pascal Pujol. Some companies are already offering a host of tests, carried out without any medical supervision. " Patients thus find themselves in possession of information about their genome, sometimes insignificant, and which they don't know what to do with. The public debate to be launched in 2018 and the revision of the bioethics law in 2019 will be an excellent opportunity to reflect medically and societally on these issues. ".

Key words : LUM#7, LUM Magazine, Medicine, Research, Health