Abstract
BackgroundC-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.Methods336 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.ResultsSix 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.ConclusionThe 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.
Highlights
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
Association of polymorphism in CCR5 promoter region with cervical cancer All these 6 single-nucleotide polymorphism (SNP) with polymorphism were in the HardyWeinberg equilibrium (HWE) in the control group (P > 0.05)
In conclusion, we demonstrated that SNPs in the CCR5 promoter are significantly associated with development of cervical intraepithelial neoplasia
Summary
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. C-C motif chemokine receptor type 5 (CCR5), a transmembrane G-coupled cell-surface chemokine receptor, binds to five kinds of CC-chemokines: human macrophage inflammatory protein-1α (MIP-1α), MIP-1β, RANTES (regulated on activation, normal T cell expressed and secreted), monocyte chemotactic protein 2 (MCP-2) and MCP-4 [1, 2]. The promoter region has been described previously [4, 5], and the differences in the promoter region may regulate the expression of CCR5 in monocyte/macrophages and T lymphocytes [5]. CCR5 expression in tumor cells and various host cells plays a very important role in tumor progression [6].
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