ABSTRACT
Some drugs are detoxified by polymorphic enzyme systems, which contributes to the great degree of variability in pharmacokinetics and toxicity; therefore, there is a need to evaluate genomic polymorphisms. Genetic instability has been recognized as a central element in the genesis of malignant lesions, resulting in clonal evolution of genetic events acquired in the course of tumor progression. A primary mechanism of action of 5-fluorouracil is inhibition of the nucleotide synthetic enzyme thymidylate synthase by its active metabolite fluorodeoxyuridine monophosphate resulting in thymidylate depletion, which if prolonged causes apoptosis via the so-called thymineless death. The p53 tumor suppressor gene is the most frequently mutated gene in all human cancers and has been described as the universal sensor of genotoxic stress. Comparative genomic hybridization identifies specific chromosomal regions that are consistently gained or lost at a high frequency within colorectal cancer and has demonstrated an increase in the genetic grade of a tumor with disease progression.
