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.
Highlights
RAD51B, a known member of the RAD51 paralogs, exerts a key role in homologous recombinational repair (HRR) of DNA double-strand breaks (DBSs) by promoting the activity of the central recombinase [1]
G allele of rs963917 showed significantly lower risk of cervical cancer compared to A allele
HRR pathway is critical for the repair of double-strand breaks (DSBs), the most harmful type of DNA damage that could lead to genome instability involved in carcinogenesis [25]
Summary
RAD51B, a known member of the RAD51 paralogs, exerts a key role in homologous recombinational repair (HRR) of DNA double-strand breaks (DBSs) by promoting the activity of the central recombinase [1]. Genomic copy number variation on chromosome 14q24.1 that includes RAD51B has been frequently detected in pedigrees with Li-F raumeni syndrome, and is associated with highly increased risk for squamous cell carcinomas [4]. The genetic variants of RAD51B may contribute to the susceptibility of cancer, as shown in the cases of breast cancer [5,6,7,8], nasopharyngeal carcinoma [9], glioma [10], and cutaneous melanoma [11]. Pedigree studies showed that cervical cancer has a significant heritability, supporting a critical role of genetic susceptibility in cervical cancer etiology [14]. Even though many studies including two genome-wide association studies (GWAS) for cervical cancer have identified susceptibility loci in CTLA4, HLA, 4q12, 17q12, etc. The missing susceptibility regions are warranted to be further explored
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