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Abstract
BackgroundAntigen-processing machinery molecules play crucial roles in infectious diseases and cancers. Studies have shown that polymorphisms in endoplasmic reticulum aminopeptidase (ERAP) genes can influence the enzymatic activity of ERAP proteins and are associated with the risk of diseases. In the current study, we evaluated the influence of ERAP gene (ERAP1 and ERAP2) polymorphisms on susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer.MethodsSix single nucleotide polymorphisms (SNPs) in ERAP1 and 5 SNPs in ERAP2 were selected and genotyped in 556 CIN patients, 1072 cervical cancer patients, and 1262 healthy control individuals. Candidate SNPs were genotyped using SNaPshot assay. And the association of these SNPs with CIN and cervical cancer was analysed.ResultsThe results showed that allelic and genotypic frequencies of rs26653 in ERAP1 were significantly different between cervical cancer and control groups (P = 0.001 and 0.004). The allelic frequencies of rs27044 in ERAP1 and rs2287988 in ERAP2 were significantly different between control and cervical cancer groups (P = 0.003 and 0.004). Inheritance model analysis showed that genotypes of rs27044, rs26618, rs26653 and rs2287988 SNPs may be associated with the risk of cervical cancer (P = 0.003, 0.004, 0.001 and 0.002). Additionally, haplotype analysis results showed that the ERAP1 haplotype, rs27044C-rs30187T-rs26618T-rs26653G-rs3734016C, was associated with a lower risk of cervical cancer (P = 0.001). The ERAP2 haplotypes rs2549782G- rs2548538A-rs2248374A-rs2287988G-rs1056893T (P = 0.009 and 0.006) and rs2549782T-rs2548538T-rs2248374G-rs2287988A-rs1056893T (P = 0.003 and 0.009) might be associated with cervical cancer and the development from CIN to cervical cancer.ConclusionOur results indicated that rs27044, rs26618 and rs26653 in ERAP1 and rs2287988 in ERAP2 influenced susceptibility to cervical cancer.
Highlights
Antigen-processing machinery molecules play crucial roles in infectious diseases and cancers
The antigen-processing machinery (APM) is composed of the proteasome, where exogenous and tumour antigens are degraded into peptides; transporters associated with antigen presentation (TAPs), which are responsible for the translocation of peptide precursors; endoplasmic reticulum aminopeptidases (ERAPs), which trim the peptides to fit major histocompatibility complex (MHC) molecules; and MHC proteins, which present antigen peptides on the cell surface [1, 2]
The results showed that the allelic and genotypic frequencies of rs26618 (P = 0.021 and 0.016, respectively), rs26653 (P = 0.001 and 0.004), rs27044 (P = 0.003 and 0.012) and rs30187 (P = 0.008 and 0.020) in ERAP1 (Table 2) and rs2248374 (P = 0.014 and 0.020) and rs2287988
Summary
Antigen-processing machinery molecules play crucial roles in infectious diseases and cancers. Studies have shown that polymorphisms in endoplasmic reticulum aminopeptidase (ERAP) genes can influence the enzymatic activity of ERAP proteins and are associated with the risk of diseases. The antigen-processing machinery (APM) is composed of the proteasome, where exogenous and tumour antigens are degraded into peptides; transporters associated with antigen presentation (TAPs), which are responsible for the translocation of peptide precursors; endoplasmic reticulum aminopeptidases (ERAPs), which trim the peptides to fit major histocompatibility complex (MHC) molecules; and MHC proteins, which present antigen peptides on the cell surface [1, 2]. Since the HLA class I antigen-presenting system is responsible for the presentation of foreign and cancerous antigens to the immune system [14, 15], and ERAPs downregulation was observed in cervical cancer [16, 17], ERAP proteins may play crucial roles in the initiation and development of cervical cancer [18]
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