title: Identification and frequency of the rs12516 and rs8176318BRCA1gene polymorphisms among different populations.
abstract: Genetic mutation of breast cancer 1 (BRCA1) is one of the most notable factors responsible for a proportion of breast cancer cases.BRCA1encodes a 1,863-amino acid protein and functions as a negative regulator of tumor growth. Thus, investigation of the underlying mechanisms that regulateBRCA1gene expression provide further insight into possible targets for breast cancer therapy. Previous studies have demonstrated that the genetic variants in theBRCA13' untranslated region (3'UTR), in addition to the cytosine-phosphate-guanine (CpG) islands in the promoter region, are significantly associated with breast cancer risk; however, the role of single nucleotide polymorphisms (SNPs) in theBRCA13'UTR remains unclear. The present study aimed to investigate the association between SNPs andBRCA1mRNA expression levels. Bioinformatics analysis demonstrated that 2 SNPs in theBRCA13'UTR (rs12516 and rs8176318 with putative microRNA binding sites) were significantly correlated with mRNA expression in lymphoblastoid cell lines (P=2.55×10-4 and P=8.78×10-5, respectively). Furthermore, the genotype frequency distribution varied between populations worldwide. In addition, 3 CpG islands and several transcription factor binding sites in theBRCA1promoter region were established. The identification of such polymorphisms and CpG islands may aid in designing improved therapeutic strategies to treat patients withBRCA1-associated breast cancer.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Fengxia
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
keywords: BRCA1; CpG islands; breast cancer; genetic polymorphism