BRIP1 variations analysis reveals their relative importance as genetic susceptibility factor for cervical cancer.

ABSTRACT

To evaluate the association between gene variations in BRIP1 (BRCA1-interacting protein 1) and the risk of cervical cancer, we examined eight single nucleotide polymorphisms (SNPs rs2048718, rs12937080, rs4988344, rs6504074, rs4988345, rs4986764, rs4986763, and rs11079454) in the BRIP1 gene in cervical tissue from a Chinese population using the MassARRAY system. The participants enrolled included 454 cervical cancer patients and 562 healthy controls. Quantitative real-time reverse transcription PCR (qRT-PCR) was performed to examine the potential correlation between functional BRIP1 SNP genotypes and mRNA levels in cervical cancer tissues. Our results first showed that rs4986764, located in exon 18 in the BRIP1 gene, was significantly associated with cervical cancer (χ(2)=11.191, P=0.001, odds ratio (OR)=1.384, 95% confidence interval (CI)=1.144-1.675). Another significant association was observed for rs4986763 located in exon 20 in BRIP1 (χ(2)=4.988, P=0.026, OR=1.241, 95% CI=1.027-1.500). Strong linkage disequilibrium was observed in the rs11079454-rs4986763-rs4986764 SNP block (D'>0.9). The frequencies of haplotype T-T-T are higher in controls than in these patients (P=2.01E-5). Moreover, cervical cancer tissues with a homozygous C/C genotype for rs4986764 had the lowest level of BRIP1, which was 2.8 and 2.9-fold lower than the C/T heterozygote and the T/T homozygote, respectively. These findings indicate a role for BRIP1 gene variations in cervical cancer and may be informative for future genetic or biological studies on cervical cancer.