RESUMEN
Breast cancer (BC) is the leading cause of death by this disease in women worldwide. Among the factors involved in tumorigenesis, long non-coding RNAs (lncRNAs) and their differential expression have been associated. Differences in gene expression may be triggered by variations in DNA sequence, including single nucleotide polymorphisms (SNPs). In the present study, we analyzed the rs527616 (C>G), located in the lncRNA AQP4-AS1, using PCR-SSP in 306 BC patients and 312 controls, from a Brazilian population. In the BC group, the frequency found for CG heterozygotes was above the expected and the overdominant model is the best one to explain our results (OR: 1.70, IC 95%: 1.23-2.34, P<0.001). Furthermore, the SNP were associated with age at BC diagnosis and the risk genotype more frequent in the older age group. According to TCGA data, AQP4-AS1 is down-regulated in BC tissue, and the overexpression is associated with better prognoses, including Luminal A, HER2-, stage 1 of disease and smaller tumor. In conclusion, the CG genotype is associated with increased susceptibility in the southern Brazilian population. This SNP is mapped in the lncRNA AQP4-AS1, showing differential expression in BC samples. Based on these results, we emphasize the potential of the role of AQP4-AS1 in cancer.
RESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) have been the target of considerable attention for their roles in many biological processes. Only a small portion of lncRNAs are functionally characterized, and several approaches have been proposed for investigating the roles of these molecules, including how polymorphisms in lncRNA genomic sites may interfere with their function. Allele frequency variation in single nucleotide polymorphisms (SNPs), for example, has been associated with several diseases, including breast cancer (BC), the most common type of cancer in women. METHODS: In the present study, we performed a systematic review of lncRNA SNPs associated with BC and a meta-analysis of some lncRNA SNPs. We found 31 SNPs mapped in 12 lncRNAs associated with BC in 28 case-control studies. RESULTS: Our meta-analysis showed an insignificant difference between the SNPs rs217727, rs3741219, rs2107425 and rs2839698 on H19, as well as rs920778, rs1899663, rs12826786 and rs4759314 on HOTAIR, and BC susceptibility. CONCLUSIONS: The present analysis recognized the importance of extensive association studies, including different populations, and further evaluation of potential functional effects caused by lncRNA SNPs. Nevertheless, genetic variants such as SNPs in lncRNAs may play many other essential roles, although this field is still under explored.