Principal Investigator: Clara Ruiz Ponte

Colorectal cancer (CRC) is one of the most common types of cancers, being the third most common type in both genders, after breast cancer in women and lung cancer in men.


As with other common diseases, CRC is considered etiologically a complex disease. This implies that the disease arises as a result of the interaction between environmental and genetic factors. That is why the study of common genetic variants has become important in recent years, as these genetic variants are expected to be responsible for CCR genetically unexplainable until now.

The most optimized and widely used strategy to detect these common genetic variants are case-control association studies. These studies compare the frequency of a particular variant between a population of affected individuals (cases) and a healthy population (controls). The differences in the prevalence of some of these variants between cases and controls might indicate that these variants are related to the onset of the disease. The use of such strategies has been driven in recent years thanks to the Human Genome Project and to the development of platforms for massive genotyping of these variants.

Thanks to this, it was also discovered that a large part of the human genome was variable and that much of this genetic variation was due to changes in one single base: the so-called single nucleotide polymorphisms or SNPs.Other forms of variation include gene rearrangements (CNVs_ Copy number variants) that may be involved in genetic susceptibility to develop diseases. In this framework, the completion of the HapMap project and the discovery of inheritance in genome blocks allowed association studies to be carried out at a genome-scale with so-called genome-wide association studies or GWAS (Genome-Wide Association Studies, from its English acronym). These allowed the study of a large number of common genetic variants scattered throughout the genome. The commercialization of GWAS was a boom in the world of genomics, enabling the identification of a large number of genetic susceptibility variants in a large number of diseases. On the other hand, it has been known for several decades now that there is a high interindividual variability in response to the administration of drugs. Some patients do not respond to treatment while others develop toxicity against it. These differences may be due to multiple factors, including age, gender, patient's health status or genetic factors. The study of the genetic variants that determine a different response to drugs is is pharmacogenetics. This science seeks to understand the genetic basis of the variability observed after administration of drugs to individualize treatments so as to improve patient response and minimize toxicity.

With this background the main objectives of this research project are:

  1. The search for new genetic susceptibility variants to CRC by GWAS studies.
  2. The analysis of genetic variability in relation to toxicity occurring in patients treated with chemotherapy CCR 5-FU and FOLFOX:

1. Regarding the first objective, we completed the analysis of one GWAS study on a Spanish population consisting of 1,548 samples which was replicated in a second phase using 3,216 samples, one of the 10 SNPs found. We are currently replicating this SNP in a third phase and are analyzing 25 other SNPs in the second phase.

2. Regarding the second objective, we completed the analysis of a GWAS study
comprising 221 patients with CRC who had received chemotherapy with 5-FU or
FOLFOX. We managed to replicate in a second stage comprised of 822 CRC patients, 3 of the 50 SNPs initially selected: two of them associated with FOLFOX / hematologic effects, and the other SNP 5Fu/ to diarrea effects.