title: Determination of CYP2D6 *3, *4, and *10 frequency in women with breast cancer in São Luís, Brazil, and its association with prognostic factors and disease-free survival.
abstract: The CYP2D6 enzyme is crucial for the metabolism of tamoxifen. The CYP2D6 gene is highly polymorphic, and individuals can be extensive, intermediate, or poor tamoxifen metabolizers. The aim of this study was to determine the frequencies of the CYP2D6 *3, *4, and *10 alleles in women with breast cancer who were treated with tamoxifen and analyze the association of enzyme activity with prognostic factors and disease-free survival. We observed a high frequency of CYP2D6 *10, with an allelic frequency of 0.14 (14.4%). The *3 allele was not present in the studied population, and *4 had an allelic frequency of 0.13 (13.8%). We conclude that patients with reduced CYP2D6 activity did not present worse tumor characteristics or decreased disease-free survival than women with normal enzyme activity, as the difference was not statistically significant. We also observed a high frequency of CYP2D6 *10, which had not been previously described in this specific population. This study is the first in north-northeastern Brazil that aimed to contribute to the knowledge of the Brazilian regional profile for CYP2D6 polymorphisms and their phenotypes. These findings add to the knowledge of the distribution of different polymorphic CYP2D6 alleles and the potential role of CYP2D6 genotyping in clinical practice prior to choosing therapeutic protocols.
authors.affiliation: Instituto Maranhense de Oncologia Aldenora Bello, São Luís, MA, Brasil.
authors.forename: D M F
authors.initials: DM
authors.lastname: Martins
authors.affiliation: Banco de Tumores e DNA do Maranhão, Universidade Federal do Maranhão, São Luís, MA, Brasil.
authors.forename: F C B
authors.initials: FC
authors.lastname: Vidal
authors.affiliation: Escola de Medicina, Universidade Federal do Maranhão, São Luís, MA, Brasil.
authors.forename: R D M
authors.initials: RD
authors.lastname: Souza
authors.affiliation: Escola de Medicina, Universidade Federal do Maranhão, São Luís, MA, Brasil.
authors.forename: S A
authors.initials: SA
authors.lastname: Brusaca
authors.affiliation: Banco de Tumores e DNA do Maranhão, Universidade Federal do Maranhão, São Luís, MA, Brasil.
authors.forename: L M O
authors.initials: LM
authors.lastname: Brito
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D019389:Cytochrome P-450 CYP2D6 / Q000145:classification / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D013629:Tamoxifen / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6