A Polymorphism rs12325489C>T in the LincRNA-ENST00000515084 Exon Was Found to Modulate Breast Cancer Risk via GWAS-Based Association Analyses

Abstract

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.

Association between RECQL5 genetic polymorphisms and susceptibility to breast cancer

“…As with most human cancers, breast cancer is a complex disease that maybe is a result of the interaction between environmental factors and genetics [5][6][7][8][9]. Previous studies indicated that DNA damage, which, if not repaired or misrepaired, may result in genomic instability, cancer transformation, or cell death [10,11].…”

Molecular aspects of breast cancer resistance to drugs (Review)

“…In fact, patients with genetic mutations in BRCA1 or BRCA2 have 30-60% likelihood of developing a second primary breast cancer and between 11 and 45% risk of ovarian cancer. Genetic variants important for evaluating an individual's risk of the disease are the protein and gene expression, microRNA, polymorphisms expression and specific epigenetic changes (13). Global hypomethylation has been observed in tumor cells together with hypermethylation in tumor suppressor genes, which inactivates certain microRNA and therefore modifies the gene expression.…”

Association between indel polymorphism (rs145204276) in the promoter region of lncRNA GAS5 and the risk of febrile convulsion

“…In particular, the CC genotype of HOTAIR rs7958904 SNP reduced the risk of colorectal tumor, whereas the TT genotype of HOTAIR rs920778 SNP elevated the risk of gastric tumors (Pan et al, ; Xue et al, ). Furthermore, an elevated risk of breast cancer is related to the CC and CT genotypes of lncRNA‐ENST00000515084 rs12325489 SNP (Li et al, ). Moreover, growth arrest special 5 (GAS5), a lncRNA located on chromosome 1q25, is suppressed in many types of tumors, such as gastric, lung, bladder, pancreatic, prostate, and breast cancer (Pickard & Williams, ).…”