Chemotherapy toxicity

Title: Genetic determinants of chemotherapy toxicity in colorectal cancer: comprehensive study of the genome. (AATRM Project 209)

Duration: 2009-12

Contractor: Catalan Agency of Technology Assessment and Research (CAHTA)

Principal Investigator: Victor Moreno

Description: Adjuvant and palliative chemotherapy treatment in colorectal cancer (CRC) is associated with unpredictable toxicity. Some polymorphisms in metabolism genes (UGT1A1, TS, DPYD) have been associated with toxicity, suggesting that other genetic factors could explain part of this toxicity. Chemotherapy could be individualized if these genetic determinants were known. The study aims to identify genetic determinants to toxicity from chemotherapy in CRC by a genome-wide scan. A two-phase design will be used. The first phase (genome-wide scan) will analyze, in a sample of 270 cases, 1.8 million of markers (SNPs and CNVs) using the Affymetrix 6.0 chip. In the second phase (validation), the most significant markers selected by various criteria and prioritized by bioinformatic methods will be validated in two independent populations, each of 400 cases. Interactions between genetic markers and clinical and pathological factors (age, sex, tumor location, stage and treatment) will be explored. We expect to identify a limited number of genes associated with toxicity. This will advance our knowledge about toxicity mechanisms of may help to design prevention strategies through the individualization of dosage or type treatment