The study that we are presenting at this meeting is a trial that we conducted in Mexico looking at mutations in the dihydropyrimidine gene, the dihydropyrimidine mutation, in people with gastrointestinal malignancies. The reason why we did this is because most panels looking at these mutations, which increase the risk for toxicities associated with fluoropyrimidines, are done in Europe or in the United States. So genetic backgrounds of other places, such as Latin America, are under-represented. So we need to understand what’s the prevalence of these mutations in other places of the world to figure out if we need to implement strategies to detect these early and avoid potentially life-threatening toxicities.

What was the methodology?

For this study we enrolled 200 consecutive patients with gastrointestinal malignancies who were candidates for receiving treatment with dihydropyrimidines. We obtained a sample, a blood sample, before starting treatment and then we did a panel, a wide panel of DPD mutations in collaboration with the National Institute of Genomics in Mexico. Then we assessed whether patients had grade 3 or higher toxicity when they were started on fluoropyrimidines. We assessed this longitudinally over six months.

What did you find?

What we found was actually very interesting and it was that the prevalence of these mutations was very low in the Mexican population. Only three patients out of the almost 200 patients we recruited had any mutation that was risky for toxicities. This is much lower than what has been found in other populations, like European populations, where you have 5% or even 10% DPD mutation. So what this shows is that the current panels and the current recommendations that we have are based on populations that are not exactly the ones that we study. So this sets the stage for future research looking into specific mutations which may be more common in Latin America and which we may need to test for if we want to implement this in these countries and in these regions.

What are the implications of these findings?

The implications are broad. Many countries in the world are not testing for this before starting treatments with fluoropyrimidines. This can be tragic because if you have a patient with these mutations and you treat them with these medications then they can have very severe toxicities that even may lead to death.

So, for example, in Europe it is by law that countries have to test for this before starting treatment. In other places, including the US, this is not done routinely. In Latin America some countries are starting to implement this but what our study shows is that if we use the panels that are designed for use in Europe we just won’t find anybody. So we have to find what the mutations are so that we can create the right panels for the right population.

Is there anything else you would like to add?

I would like to thank the American Gastroenterological Association which funded this study through a disparities grant that was sent out last year. This was very important because it was the first time one of these grants was given for research outside of the United States so I would like to acknowledge their support.