Revisión bibliográfica de los polimorfismos genéticos asociados a toxicidad en el tratamiento con 5-fluorouracilo en pacientes con cáncer colorrectal

Abstract

Colorectal cancer is the most common malignancy of the digestive tract. It can be localized from the Ileocecal valve to the rectum. Colon cancer is the second most common cause of death, after lung cancer in men and breast cancer in women. The process involved in the development of colon cancer is caused mainly by alteration of synthesis and repair of the DNA. The treatment is based basically on the administration of antitumor medications, like 5- fluorouracil (5-FU) that belongs to the class of antimetabolites antineoplastic agents. However, it has been shown that there is toxicity related with genetic polymorphism in patients treated with 5-FU, including gastrointestinal symptoms, myelosuppression and neurotoxicity. The genetic polymorphism can affect the protein expression, the enzymatic activity, substrate binding and signaling pathways; the genetic variations of four main genes have been studied, including ABCB1, DPYD, MTHFR and TYMS. OBJECTIVE: Establish the genetic polymorphism associated with the toxicity with the use of 5-fluorouracil in patients with colorectal cancer. METHODOLOGY: Bibliographic review based on digital articles, starting with the research of information about 5-fluorouracil as treatment of patients with colorectal cancer, its adverse reactions, polymorphisms and toxicity. The data base used are: PubMed, ScienceDirect and Scielo; published within the last 10 years. It included scientific articles and studies done in patients older than 18 years old. Publications in Spanish and English as well as full text articles. Additionally, the polymorphisms were analyzed in the NCBI (National Center for Biotechnology Information) database, from which the allelic frequencies at the global and Latin American levels were obtained. RESULTS: A total of 11 articles were reviewed, from where we obtained data about polymorphism that developed in patients with colorectal cancer who receive treatment with 5-fluorouracil. The genes that were analyzed are: ABCB1, DPYD, MTHFR y TYMS, with their respective variations. It was established that the polymorphisms trigger toxicity that manifests itself in different forms: diarrhea, stomatitis, mucositis, neutropenia, etc.