Resumo

CORTEJOSO, L. et al. Validation of genetic polymorphisms associated to the toxicity of chemotherapy in colorectal cancer patients. Farm Hosp. [online]. 2014, vol.38, n.4, pp.283-290. ISSN 2171-8695.  https://dx.doi.org/10.7399/FH.2014.38.4.1121.

Objective: To validate the associations previously found in three cohorts of patients from the General University Hospital Gregorio Maranon, between the polymorphisms rs1128503, rs2032582 and rs1045642 of the ABCB1 gene and the hand-foot syndrome and diarrhea in colorectal cancer patients treated with chemotherapy regimes containing Capecitabine and 5-Fluorouracil, respectively, and between the polymorphisms rs2297595 of the DPYD gene and nausea/vomiting, rs11615 of ERCC1 and neutropenia, and rs28399433 CYP2A6 and neutropenia, in colorectal cancer patients treated with FOLFOX or XELOX as adjuvant therapy. Method: Colorectal cancer patients treated with chemotherapy regimes, containing Capecitabine (n = 157), 5-Fluorouracil (n = 99) were included in the study, as well as patients treated with XELOX or FOLFOX (n = 83) as adjuvant therapy. The patients included were recruited from the Doce de Octubre University Hospital and from the Gregorio Maranon General University Hospital, and signed the informed consent form. DNA was obtained from blood samples. Genotyping was carried out with SNaPshot. Contingency tables were created for analyzing the associations between the genotypes and the adverse reactions. Results: None of the associations previously identified was replicated in the validation cohort. Conclusions: Pharmacogenetic studies with a limited sample size must be validated with bigger cohorts, if possible by means of multicentre studies, reducing the variables to the maximum and should never be used in clinical practice without validation.

Palavras-chave : Biomarkers; Toxicity; Chemotherapy; Colorectal cancer; Validation; Pharmacogenetics.

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