Polymorphisms in the CCR5 promoter associated with cervical intraepithelial neoplasia in a Chinese Han population

Abstract

Abstract Background C-C chemokine receptor 5 (CCR5) has attracted wide concern for its critical role in the progression of human immunodeficiency virus type 1 (HIV-1) infection. Several studies have demonstrated that CCR5 affects the processes of tumor cell migration, invasion, and metastasis. The aim of this study was to illustrate the association between the polymorphisms of the CCR5 promoter and the development of cervical cancer. Methods 336 women with cervical intraepithelial neoplasia (CIN), 488 women with cervical cancer (CC), and 682 healthy controls were recruited to detect polymorphisms in the CCR5 promoter using a sequencing method. Results Six loci with polymorphism were found in the CCR5 promoter; the frequencies of the minor alleles of rs1799987 was significantly higher in the CIN group than that in the control group (P = 0.007); and the genotypic frequencies of rs2734648, rs1799987, rs1799988 and rs1800023 were significantly different between the CIN group and the control group (P < 0.008). The inheritance model analysis showed that rs2734648, rs1799987, rs1799988 and rs1800023 significantly increased the susceptibility to CIN in a recessive genetic model (P < 0.008). The haplotype constructed by the major alleles of these 6 SNPs (rs2227010-rs1799987-rs1799988-rs2734648-rs1800023-rs1800024: A-G-A-C-A-T) was highly protective against CIN (OR = 0.731, 95%CI: 0.603–0.886, P = 5.68E-03). In addition, transcription prediction showed that mutation of these 6 SNPs might alternate the binding of particular transcription factors. Conclusion The CCR5 promoter polymorphisms were significantly associated with cervical intraepithelial neoplasia by altering the expression of CCR5 on the cell surface in a Chinese Han population.

Keywords

• Cervical carcinogenesis
• Cervical intraepithelial neoplasia
• CCR5 gene
• Promoter polymorphism