Polymorphisms in endoplasmic reticulum aminopeptidase genes are associated with cervical cancer risk in a Chinese Han population

Abstract

Background: antigen-processing machinery molecules play crucial roles in infectious diseases and cancers. Studies have shown that variants in endoplasmic reticulum aminopeptidase (ERAP) genes can influence the enzymatic activity of ERAP proteins and are associated with the risk of cancers. In the current study, we evaluated the influence of ERAP gene (ERAP1 and ERAP2) variants on susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer.Methods: Six 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.Results: the 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 also significantly different between control and cervical cancer groups (P=0.003 and 0.004). Inheritance model analysis showed that genotypes at rs26618, rs26653, rs27044, and rs2287988 SNPs may be associated with the risk of cervical cancer (P=0.004, 0.001, 0.003, and 0.002). Additionally, haplotype analysis results showed that the ERAP1 haplotype, rs26618T-rs26653G-rs27044C-rs30187T-rs3734016C, was associated with a lower risk of cervical cancer (P=0.001; OR=0.804, 95%CI:0.711-0.910). The ERAP2 haplotypes rs2248374A-rs2549782G-rs2287988G-rs2548538A-rs1056893T might be the risk factor of cervical cancer (P=0.009; OR=1.592, 95%CI:1.122-2.258). Haplotype rs2248374G-rs2549782T-rs2287988A-rs2548538T-rs1056893T of ERAP2 might be associated with lower risk of cervical cancer (P=0.003; OR=0.835,95%CI:0.740-0.942). Conclusion: Our results indicated that rs26653 and rs27044 in ERAP1 and rs2287988 in ERAP2 influenced susceptibility to cervical cancer.