Genetic variants within microRNA‐binding site of RAD51B are associated with risk of cervical cancer in Chinese women

Abstract

RAD51B plays a central role in homologous recombinational repair (HRR) of DNA double‐strand breaks (DSBs), which is important to prevent genomic instability, a hallmark of cancer. Recent studies suggested that common genetic variants of RAD51B may contribute to cancer susceptibility. In this study, we aimed to investigate whether potentially functional variants within miRNA‐binding sites of RAD51B are associated with risk of cervical cancer. A total of 1486 cervical cancer patients and 1536 cancer‐free controls were enrolled, and two genetic variants, rs963917 (A > G) and rs963918 (T > C), were genotyped in all participants. Using multivariate logistic regression analyses, we found that G allele of rs963917 conferred lower risk of cervical cancer compared to A allele (adjusted OR = 0.89, 95% CI = 0.80–0.99, P = 0.039). Similarly, rs963918 allele C was associated with a decreased risk for cervical cancer compared with allele T (adjusted OR = 0.84, 95% CI = 0.74–0.94, P = 0.004). Haplotype analyses showed that haplotype GC was also correlated with lower risk (OR = 0.83, 95% CI = 0.73–0.95, P = 0.005) compared with the most common haplotype AT. In summary, our study suggested that miRNA‐binding site genetic variants of RAD51B may modify the susceptibility to cervical cancer, which is important to identify individuals with differential risk for this malignancy and to improve the effectiveness of preventive intervention.

Identification of Prognostic miRNA Signature and Lymph Node Metastasis-Related Key Genes in Cervical Cancer

“…RAD51B is one of the RAD51 gene families involved in homologous recombination-mediated DNA repair (Thacker, 2005;Nagathihalli and Nagaraju, 2011). Hang et al (2016) demonstrated that RAD51B is a tumor suppressor gene in cervical cancer cells, which is consistent with our prediction. They further showed that the miRNA binding sites of RAD51B genetic variants in cervical cancer cells may increase tumor susceptibility, and RAD51B is vital in gauging the cervical cancer risk of individuals and improving the effectiveness of preventive intervention (Hang et al, 2016).…”

“…The decreased expression of CXCL12 in cervical cancer cells and its role in lymph node metastasis was confirmed in previous experiments (Yadav et al, 2016), and the decreased expression of IGF1 and the increased expression of WDHD1 were also experimentally validated in cervical cancer cells but only in lymph node metastasis of other cancers (Serrano et al, 2006;Kümmel et al, 2007;Huang et al, 2008;Zhou et al, 2016;Liu et al, 2019). Interestingly, the expression of RAD51B is also decreased in cervical cancer cells, but experiments showed that its expression is increased in other cancer lymph node metastases (Cheng et al, 2016;Hang et al, 2016). In addition, REV3L expression is increased in cervical cancer cells and lymph node metastases of other cancers in the laboratory, which is inconsistent with our prediction results (Yang et al, 2015;Zhu et al, 2016).…”

Role of long non-coding RNAs in disease progression of early stage unmutated chronic lymphocytic leukemia

“…In gastric cancer, RAD51B specifically has been identified as a potential biomarker for poor prognosis [61]. Furthermore, genetic variants in miR-binding sites of RAD51B have been shown to be associated with cervical cancer risk [62]. While germline mutations in RAD51B do not contribute to CLL [63], lack of lncRNA expression may be contributing to RAD51B expression and thus contributing to disease progression.…”

Systematic analysis of genetic variants in cancer-testis genes identified two novel lung cancer susceptibility loci in Chinese population

“…In this study, genotyping in the validation stage was performed using the Sequenom MassARRAY iPLEX platform (Sequenom Inc. San Diego, CA, USA) according to the protocol [15,16]. Primers for 17 out of 20 candidate SNPs were successfully constructed.…”