[en] Background: DNA repair is a fundamental mechanism for maintaining genome integrity of individuals and the deficit has been associated with different forms of cancer. On the other hand, many of the treatments used against these tumors, tumors act through direct induction of DNA damage and repair of these injuries is considered one of the main mechanisms of resistance to these drugs. Polymorphisms in DNA repair genes that condition a decrease in its function have been associated with both breast cancer risk (CM) and responses to different forms of treatment. To analyze the relationship XRCC3Thr241Met, XPDLys751Gln XRCC1Arg399Gln and the risk of breast cancer, age at diagnosis and response to treatment. Methods: We conducted an association study of cases and controls, and independently, a radio studio and genomic medicine. We included 174 women with CM and 300 controls. Germline DNA genotyping was performed by PCR-RFLP and Q-PCR. Results: The allele XRCC1Arg399Gln Gln was more frequent among cases than controls, associated with an increased risk of CM (p = 0.002, OR: 1.96. 95% CI 1.3-3). The alleles which have better repair capacity associated with the diagnosis of CM at later ages, but the difference was statistically significant only for XPD751Lys/Lys. None of the polymorphisms was associated with acute or chronic skin toxicity after RT XRCC3241Met/Met XRCC1399Arg/Arg and were associated with better disease free survival (p = 0.007, HR: 0.4, 95% CI 0.2 to 0.9) and overall survival (p = 0.027, HR: 0.15, 95% from 0.02 to 0.99) respectively, in patients with early-stage CM treated with anthracyclines. Conclusions: XRCC1399Gln is associated with risk of CM. XPD751Lys/Lys, is associated with the diagnosis of CM at later ages. XRCC1Arg399Gln could XRCC3Thr241Met and pharmacogenomic implications for selecting the most appropriate treatment for patients with CM in early stages.

[es] Introducci?n: La reparaci?n del ADN es un mecanismo fundamental para mantener la integridad del genoma de los individuos y su d?ficit se ha asociado con diferentes formas de cancer. Por otro lado, muchos de los tratamientos que se emplean contra estos tumores tumores act?an mediante la inducci?n directa del da?o al ADN, y la reparaci?n de estas lesiones se considera uno de los principales mecanismos de resistencia a estos f?rmacos. Polimorfismos en los genes reparadores del ADN que condicionen una disminuci?n de su funci?n se han asociado tanto al riesgo de cancer de mama (CM) como a la respuesta a diferentes formas de tratamiento. Objetivos: Analizar la relaci?n de XRCC3Thr241Met, XRCC1Arg399Gln y XPDLys751Gln con el riesgo de cancer de mama, la edad al diagnostico y la respuesta al tratamiento. M?todos: Se realizo un estudio de asociaci?n de casos y controles, e independientemente, un estudio f?rmaco y radio-gen?mico. Se incluyeron 174 mujeres con CM y 300 controles. El genotipado del ADN germinal se realizo mediante PCR-RFLP y Q-PCR. Resultados: El alelo Gln de XRCC1Arg399Gln fue m?s frecuente entre los casos que en los controles, asoci?ndose a un incremento del riesgo de CM (p=0.002, OR:1.96. IC95%1.3-3). Los alelos que presentan mejor capacidad de reparaci?n se asociaron al diagn?stico de CM a edades m?s tard?as, pero la diferencia solo fue estad?sticamente significativa para XPD751Lys/Lys. Ninguno de los polimorfismos se asoci? con la toxicidad cut?nea aguda o cr?nica tras RT XRCC1399Arg/Arg y XRCC3241Met/Met se asociaron a mejor Supervivencia Libre de Enfermedad (p=0.007, HR: 0.4, IC95%0.2-0.9) y Supervivencia Global (p=0.027, HR:0.15, IC95% 0.02-0.99) respectivamente, en pacientes con CM en estadio precoz tratadas con antraciclinas. Conclusiones: XRCC1399Gln se asocia con el riesgo de CM. XPD751Lys/Lys, se asocia con el diagn?stico de CM a edades m?s tard?as . XRCC3Thr241Met y XRCC1Arg399Gln podr?an implicaciones farmacogenomicas para seleccionar el tratamiento m?s adecuado para las pacientes con CM en estadios precoces.