ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer

Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis. A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico-pathologic parameters were compared. We found a significant association of rs1800544 GG genotype with young age at diagnosis, premenopausal status, higher tumor size, metastasis in lymph nodes, advanced TNM stages and higher Nottingham Prognosis Indicator (NPI) (p < 0.05). There was no association between rs1800544 and SBR stages, Her2, ER and PR statuses and the molecular classification. The rs553668 AA genotype was associated to young age at diagnosis and premenopausal status (p < 0.05). The haplotype GA was associated to the early age of diagnosis (p = 0.03), and the haplotype GG to higher tumor size, lymph node involvement, advanced TNM stages and Her2 positive status (p < 0.05). There was no polymorphism or haplotype association with BC risk (p > 0.05). ADRA2A polymorphism is associated with indicators BC poor prognosis but not with BC susceptibility. This is the first report suggesting that ADRA2A germline gene polymorphism could represent a predictor factor for BC outcome. Further investigation of other ADRA2A polymorphisms in BC risk or prognosis are needed and may lead to a genotype-based therapy.