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A Polymorphism rs12325489CT in the LincRNA-ENST00000515084 Exon Was Found to Modulate Breast Cancer Risk via GWAS-Based Association Analyses
Ist Teil von
PloS one, 2014-05, Vol.9 (5)
Ort / Verlag
Public Library of Science
Erscheinungsjahr
2014
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Breast cancer, one of the most common malignancies diagnosed among women worldwide, is a complex polygenic disease in the etiology of which genetic factors play an important role. Thus far, a subset of breast cancer genetic susceptibility loci has been addressed among Asian woman through genome-wide association studies (GWASs). In this study, we identified numerous long, intergenic, noncoding RNAs (lincRNAs) enriched in these breast cancer risk-related loci and identified 16 single nucleotide polymorphisms (SNPs) located within the sequences of lincRNA exonic regions. We examined whether these 16 SNPs are associated with breast cancer risk in 2539 cancer patients and 2818 control subjects from eastern, southern, and northern Chinese populations. We found that the C allele of the rs12325489C>T polymorphism in the exonic regions of lincRNA-ENST00000515084 was associated with a significantly increased risk of breast cancer (adjusted odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.50-2.12), compared with the rs12325489TT genotype. Biochemical analysis demonstrated that the C to T base change at rs12325489C>T disrupts the binding site for miRNA-370, thereby influencing the transcriptional activity of lincRNA-ENST00000515084 in vitro and in vivo, and affecting cell proliferation and tumor growth. Our findings indicate that the rs12325489C>T polymorphism in the lincRNA-ENST00000515084 exon may be a genetic modifier in the development of breast cancer.