RESUMO
Breast-conserving surgery followed by radiotherapy is effective in reducing recurrence; however, telangiectasia and fibrosis can occur as late skin side effects. As radiotherapy acts through producing DNA damage, we investigated whether genetic variation in DNA repair and damage response confers increased susceptibility to develop late normal skin complications. Breast cancer patients who received radiotherapy after breast-conserving surgery were examined for late complications of radiotherapy after a median follow-up time of 51 months. Polymorphisms in genes involved in DNA repair (APEX1, XRCC1, XRCC2, XRCC3, XPD) and damage response (TP53, P21) were determined. Associations between telangiectasia and genotypes were assessed among 409 patients, using multivariate logistic regression. A total of 131 patients presented with telangiectasia and 28 patients with fibrosis. Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia. The odds ratios (OR) were 1.66 (95% confidence interval (CI): 1.02-2.72) for 72Pro carriers and 1.95 (95% CI: 1.13-3.35) for PIN3 A2 allele carriers compared with non-carriers. The TP53 haplotype containing both variant alleles was associated with almost a two-fold increase in risk (OR 1.97, 95% CI: 1.11-3.52) for telangiectasia. Variants in the TP53 gene may therefore modify the risk of late skin toxicity after radiotherapy.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Dano ao DNA/genética , Reparo do DNA/genética , Polimorfismo Genético , Lesões por Radiação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Terapia Combinada/efeitos adversos , Dano ao DNA/fisiologia , Feminino , Seguimentos , Genes p53 , Haplótipos , Humanos , Desequilíbrio de Ligação , Mastectomia Segmentar/reabilitação , Pessoa de Meia-Idade , Polimorfismo Genético/fisiologia , Polimorfismo de Nucleotídeo Único , Lesões por Radiação/complicações , Lesões por Radiação/patologia , Dermatopatias/etiologia , Dermatopatias/genéticaRESUMO
In a population-based study of 613 cases and 1082 controls, alcohol dehydrogenase 1B (ADH1B) genotype was not an independent risk factor for breast cancer, although the possibility was raised that it modifies risk associated with high levels of alcohol consumption (OR 1.1, 95% confidence interval (CI) 0.8-1.6 for ADH1B*1/*1 genotype vs 0.2, 95% CI 0.1-1.0 for ADH1B*2 carriers).
