A Genetic Polymorphism (rs17251221) in the Calcium-Sensing Receptor is Associated with Breast Cancer Susceptibility and Prognosis

Background: Calcium-sensing receptor (CaSR) is a typical G protein coupled receptor. The rs17251221 SNP is located in an intron of the CaSR gene, and the G allele is considered a gain of function mutation. Previous studies revealed that rs17251221 polymorphisms contribute to the risk of developing certain types of cancers. This study investigated the rs17251221 SNP in breast cancer by analyzing the correlation of the rs17251221 genotype with breast cancer susceptibility, clinicopathological features and prognosis. Methods: A TaqMan assay was used to genotype the rs17251221 SNP in a case-control study. The expression levels of CaSR in breast cancer tissues were determined using quantitative reverse-transcription PCR (qRT-PCR) and western blot analysis. The association of the rs17251221 genotype and the clinicopathological characteristics, as well as the prognosis of the breast cancer patient, was assessed statistically. Results: We found that the AG and GG genotypes were associated with lower mRNA and protein levels of CaSR compared to the AA genotype in breast cancer tissues. We also found that the AG and GG genotypes were associated with breast cancer susceptibility, the patient's age at diagnosis, tumor size, lymph node metastasis and estrogen receptor status of breast cancer tissue. More importantly, we found that the genotypes were prognostic markers for both disease-free survival and overall survival of breast cancer. Conclusion: The rs17251221 SNP is a risk factor associated with breast cancer susceptibility, as well as a prognostic indicator. Our data suggest that rs17251221 may be a potential therapeutic target in breast cancer.