Recently, numerous researchers have concentrated on elucidating the correlations between lncRNAs and the susceptibility to BC. For example, Li et al carried out a GWAS-based association analysis between lncRNAs and BC prevalence, which suggested that lncRNAs polymorphism was linked to a higher BC risk probably via influencing microRNA-mediated regulation in cell processes. In this work, we performed the association analyses between LOC105371267 polymorphisms and the risk of BC based on a Chinese population. Five candidate SNPs (rs6499221, rs3931698, rs8044565, rs3852740 and rs111577197) were successfully genotyped. We found that carriers with rs3931698-G allele might have a lower incidence of BC. Stratified by age, rs6499221 increased BC risk while rs3931698 reduced the risk at age < 52 years. Meanwhile, a higher risk was observed between rs3931698SNP and other two clinical indicators (PR status and stage). Rs6499221 and rs3852740 polymorphisms showed a decreased risk in ER-positive patients. Therefore, we speculated that LOC105371267 with SNPs (rs6499221, rs3931698, rs8044565 and rs3852740) might be responsible for the occurrence and development of BC. However, no significant relationship was found between LOC105371267 rs111577197 and BC prevalence.
LOC105371267 (also known as PR-lncRNA1) was reported to be a p53-regulated lncRNA. Sánchez et al highlighted that LOC105371267 could enhance cell apoptosis and cell cycle arrest by promoting the p53 signaling activation. Specifically, they argued that PR-lncRNA1 regulated the p53 transcriptional network by the efficient binding of p53 to some of its target genes. Furthermore, Li et al previously also pinpointed that PR-lncRNA1 interacted with a sequence-specific RNA binding protein Sam68 and this complex could promote the p53-mediated transcription in human colon carcinoma cell lines . These lines of evidence have led us to formulate the hypothesis that PR-lncRNA1 could be of pathogenic importance in BC. Our results firstly revealed that LOC105371267 polymorphisms were associated with the susceptibility to BC.
Age has been identified as a prominent risk factor in the BC initiation . An early study suggested that BC patients with the oldest age were more vulnerable to rapid deterioration . Moreover, Unlu et al highlighted that older women tend to have a higher BC risk compared with those younger women . In the study, we found that PR-lncRNA1 SNP rs6499221 and rs3931698 were related to the risk of BC patients at age < 52 years. Additionally, several clinicopathological characteristics, including ER, PR, Ki-67, metastasis, stage and tumor size were also observed to participate in the BC pathogenesis [21–23]. Our study found that LOC105371267 polymorphisms might be associated with ER, PR, and stage of BC.
Although the association of four SNPs in PR-lncRNA1 with BC risk and several clinicopathological characteristics have been identified in the present work, there are still limitations. On the top of that, due to all participants were all enrolled in the same hospital and were Chinese Han population, the inherent selection bias cannot be excluded and our results cannot permit extrapolation of the results to other ethnic groups. In addition, the comprehensive clinical information and environmental factors should be included. Moreover, the precise molecular mechanisms of PR-lncRNA1 polymorphisms in BC progression remain to be deciphered. Despite the limitations mentioned above, the results of our study might provide evidence for the future studies about LOC105371267 with BC.