RESUMEN
The DNA repair pathway is known to play a role in the etiology of breast cancer. A number of studies have demonstrated that common germline variants in genes involved in the DNA repair pathway influence breast cancer risk. To assess whether alterations in DNA repair genes contribute to breast cancer, we genotyped 12 single nucleotide polymorphisms (SNPs) in 1,109 Cypriot women with breast cancer and 1,177 age-matched healthy controls. We found significant associations with breast cancer for SNPs in the BRCA2 and MRE11A genes. Carriers of the BRCA2 rs1799944 variant (991 Asp) were found to have an increased risk of breast cancer (OR = 1.41, 95% CI 1.08-1.83, P = 0.01) with P (trend) = 0.0076. Homozygous carriers of the MRE11A rs601341 A allele had an increased risk of breast cancer (OR = 1.36, 95% CI 1.08-1.71, P = 0.009) with P (trend) = 0.0087. This study suggests that genetic variants in BRCA2 and MRE11A are associated with breast cancer risk.
Asunto(s)
Neoplasias de la Mama/genética , Enzimas Reparadoras del ADN/genética , Reparación del ADN , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Chipre/epidemiología , Proteínas de Unión al ADN/genética , Femenino , Homocigoto , Humanos , Proteína Homóloga de MRE11 , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de RiesgoRESUMEN
Population-based studies have reported significant associations between specific genetic polymorphisms and breast cancer susceptibility. A number of studies have demonstrated that common variants of genes involved in the DNA repair pathway act as low penetrance breast cancer susceptibility alleles. We aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the DNA repair genes XRCC1, XRCC2 and XRCC3 and breast cancer in MASTOS, a population-based case-control study of 1,109 Cypriot women with breast cancer diagnosed between 40 and 70 years and 1,177 age-matched healthy controls. Five coding SNPs were genotyped including rs1799782, rs25489 and rs25487 in XRCC1, rs3218536 in XRCC2 and rs861539 in XRCC3. Homozygous XRCC1 280His carriers had an increased risk of breast cancer (odds ratio 4.68; 95% CI 1.01-21.7; P = 0.03). The XRCC2 188His allele was associated with a marginal protective effect for breast cancer (odds ratio 0.79; 95% CI 0.62-1.00; P = 0.05). No significant associations were observed between the other three SNPs and breast cancer. This study suggests that genetic variation in SNPs in XRCC1 and XRCC2 genes may influence breast cancer susceptibility.