Pharmacogenetics findings in Brazilian cancer patients.

Abstract

e13607 Background: Pharmacogenetic is the study of genetic modifications influence on drugs action. Recent studies have suggested that some genetic polymorphisms may have an influence on patient outcomes. Thus, the objective of this thesis is to evaluate the frequency of genetic polymorphisms in cancer patients. Methods: Cross-sectional study at the Oncology Center of São Paulo. The reports presented a SNP evaluation (saliva - PCR-Multiplex, PCR-RFLP or capillary sequencing - Genotypic variants: 1 allele, 2 alleles and no allelic alteration). Polymorphs were validated according to the localized gene and its relationship to drugs using PharmGKB, NCBI SNP Database, NCBI Gene Database and DrugBank Database. Results: Sample mean aging was 49.92 years (SD = 22.73), with breast cancer (n = 26 /% = 26.3) and stage IV (n = 51 /% = 51.6). Among the evaluated platinum components, it is possible to verify that the presence of polymorphisms was more frequent. Of these, all had the highest frequency of polymorphisms in only 1 allele (xpc__rs2228001 = 25.4%; ercc1_rs11615 = 21.2%; xrcc3_rs861539 = 22.2%; mthfr_rs1801133 = 44.4%). This was repeated when evaluating the Cyclophosphamide, Fluoropyrimidines, Taxanes, Anastrozole and Epirubicin-related polymorphisms. When we evaluated the Tamoxifen-related genes, the polymorphisms absence was more frequent (cyp2d6_rs3892097 = 26.3%; cyp3a4_rs2740574 = 61.6%). Evaluating all medications the highest frequency was polymorphism in only 1 allele. Consequently, for the irinotecan drug evaluation, two polymorphisms were evaluated and presence of polymorphism (xrcc3_rs861539 = 58%), mostly in only 1 allele (44%). Conclusions: Therefore we can evaluate that the allelic frequency variability of the polymorphs observed, despite the great variability, shows most evaluated individuals present some type of genotypic modification, being the majority in only 1 allele.