Frequency of 14 genetic variants associated with breast cancer risk and treatment in a Colombian population / Frecuencia de 14 variantes genéticas asociadas con el riesgo y el tratamiento del cáncer de mama en una población colombiana

ABSTRACT

SUMMARY Introduction: Genetic variations have been related to risk and treatment efficacy. Many polymorphisms in breast cancer are known to influence susceptibility, breast cancer risk and treatment outcome. Polymorphisms vary among populations; therefore, local studies are necessary. Objective: To establish the frequency of polymorphisms associated to breast cancer risk and treatment pharmacogenomics in a group of Colombian individuals. Methods: Data from microarray profiles including gene polymorphisms associated with breast cancer treatment were retrospectively collected (Pathway Genomics®). The frequency of marker CYP2D6 rs3892097 and a breast cancer panel (CAS8 rs1045485, CHEK21100delC, ESR1 rs2046210, FGFR2 rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, AKAP9 rs6964587, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 delT, ESR1 rs3020314) were studied. Results: Microarray data from 68 men and 92 women were analyzed. All polymorphisms were in Hardy-Weinberg equilibrium. Genotypic frequencies of CYP2D6 rs3892097 C/T, CAS8 rs1045485 G/C, and those of genes included in a breast cancer panel (CAS8 rs1045485, CHEK21100delC, FGFR2rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 del T, ESR1rs3020314) did not significantly differ from previously published data. ESR1 rs2046210, with allele frequencies of C=0.04 and T=0.02, and AKAP9 rs6964587, with a frequency of A=0.005, were determined as rare. Conclusions: The population studied was not significantly different in allele distribution from previously reported data at HapMap. Genotypes in Colombian population are similar to other previously studied groups of healthy subjects. Extended use of genotyping pharmacogenetic polymorphisms will prevent toxicity and adverse effects in tamoxifen treatment (for example in CYP2D6 rs3892097). Therefore, therapeutic alternatives should be evaluated based on individual pharmacogenetic studies.

RESUMEN

RESUMEN Introducción: las variaciones genéticas se han relacionado con el riesgo y la eicacia del tratamiento. Es sabido que muchos polimorfismos en cáncer de mama influyen en la susceptibilidad, el riesgo de cáncer y el resultado del tratamiento. Los polimorfismos varían entre las poblaciones, y por tanto, es necesario realizar estudios locales. Objetivo: establecer la frecuencia de polimorismos asociados al riesgo de cáncer de mama y la farmacogenómica del tratamiento en un grupo de individuos colombianos. Métodos: los datos de los perfiles de microarreglos, incluidos los polimorismos genéticos asociados con el tratamiento del cáncer de mama, se obtuvieron de forma retrospectiva (Pathway Genomics®). Se estudiaron la frecuencia del marcador CYP2D6 rs3892097 y un panel de cáncer de mama (CAS8 rs1045485, CHEK21100delC, ESR1 rs2046210,FGFR2 rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, AKAP9 rs6964587, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 delT, ESR1 rs3020314). Resultados: se analizaron los datos de microarreglos de 68 hombres y 92 mujeres. Todos los polimorfismos siguieron el equilibrio Hardy-Weinberg. Las frecuencias fenotípicas de CYP2D6 rs3892097 C/T, CAS8 rs1045485 G/C, y aquellas de los genes incluidos en un panel de cáncer de mama (CAS8 rs1045485, CHEK21100delC, FGFR2rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 del T, ESR1rs3020314) no difirieron significativamente de los datos publicados previamente. ESR1 rs2046210, con frecuencias alélicas de C = 0,04 y T = 0,02, y AKAP9 rs6964587, con una frecuencia de A = 0,005, se determinaron como raras.