Hang Dong, Zhou Wen, Jia Meiqun, Wang Lihua, Zhou Jing, Yin Yin, Ma Hongxia, Hu Zhibin, Li Ni, Shen Hongbin
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Cancer Med. 2016 Sep;5(9):2596-601. doi: 10.1002/cam4.797. Epub 2016 Jun 23.
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.
RAD51B在DNA双链断裂(DSB)的同源重组修复(HRR)中起核心作用,这对于预防基因组不稳定(癌症的一个标志)很重要。最近的研究表明,RAD51B的常见基因变异可能与癌症易感性有关。在本研究中,我们旨在调查RAD51B的miRNA结合位点内潜在的功能性变异是否与宫颈癌风险相关。共纳入了1486例宫颈癌患者和1536例无癌对照,并对所有参与者的两个基因变异rs963917(A>G)和rs963918(T>C)进行基因分型。使用多因素逻辑回归分析,我们发现rs963917的G等位基因与A等位基因相比,宫颈癌风险较低(校正OR=0.89,95%CI=0.80-0.99,P=0.039)。同样,与T等位基因相比,rs963918的C等位基因与宫颈癌风险降低相关(校正OR=0.84,95%CI=0.74-0.94,P=0.004)。单倍型分析表明,与最常见的单倍型AT相比,单倍型GC也与较低风险相关(OR=0.83,95%CI=0.73-0.95,P=0.005)。总之,我们的研究表明,RAD51B的miRNA结合位点基因变异可能会改变宫颈癌的易感性,这对于识别该恶性肿瘤风险不同的个体以及提高预防干预的有效性很重要。