Mutational Analysis of Oncogenic AKT1 Gene Associated with Breast Cancer Risk in the High Altitude Ecuadorian Mestizo Population.

Breast cancer is the leading cause of cancer-related death among women worldwide. AKT1 encodes the kinase B alpha protein. The rs121434592, rs12881616, rs11555432, rs11555431, rs2494732, and rs3803304 single nucleotide polymorphisms have been identified in the AKT1 kinase gene. Activated AKT1 phosphorylates downstream substrates regulating cell growth, metabolism, apoptosis, angiogenesis, and drug responses. It is essential to know how breast cancer risk is associated with histopathological and immunohistochemical characteristics and genotype polymorphisms in a high altitude Ecuadorian mestizo population. This is a retrospective case-control study. DNA was extracted from 185 healthy and 91 affected women who live 2,800 meters above sea level. Genotypes were determined by genomic sequencing. We found a possible association between the noncoding intronic variant rs3803304 and breast cancer risk development: GG (odds ratio [OR] = 5.2; 95% confidence interval [CI] = 1.3-20.9; P ≤ 0.05; Q > 0.05). Regarding pathologic characteristics, we found significant risk between estrogen receptor, progesterone receptor, and HER2 status and molecular subtypes ( P ≤ 0.001; Q ≤ 0.05). On the other hand, we did not find risk between variants and histopathological characteristics. Despite the small sample size, we found that the intronic variant, AKT1 rs3803304, may act as a predictive biomarker in the risk of developing breast cancer in the high altitude Ecuadorian mestizo population.