Abstract
An effective cytotoxic immune response to neoplastic cells requires efficient presentation of antigenic peptides to T lymphocytes by HLA class I (HLA-I) molecules. The HLA-I-bound peptide repertoire depends on antigen-processing machinery molecules. Aminopeptidase residing in endoplasmic reticulum 1 (ERAP1) trims peptides to the optimal length for HLA-I binding. Single nucleotide polymorphisms (SNPs) in the ERAP1 gene result in changes in aminopeptidase activity and specificity. This may affect susceptibility to cancer. However, non-small cell lung carcinoma (NSCLC) has not been studied in this respect. We compared genotype and haplotype frequencies of four coding, nonsynonymous ERAP1 SNPs, rs26653G > C, rs26618T > C, rs30187C > T, and rs27044C > G, in NSCLC occurring in two genetically distant populations, Chinese and Poles. We found associations of all four SNPs with NSCLC in Chinese but not in Poles. The differences in ERAP1-NSCLC associations might be explained by highly significant differences in SNP genotype frequencies between Chinese and Poles (except for rs26618). In accordance with this, the most frequent ERAP1 haplotypes were distributed differently in cases versus controls in Chinese, but not in Poles. Our findings add to the differences between Orientals and Caucasians in genetics of disease susceptibility.Electronic supplementary materialThe online version of this article (doi:10.1007/s00005-016-0436-4) contains supplementary material, which is available to authorized users.
Highlights
Eradication of tumor cells is mediated by CD8? cytotoxic T cells, which recognize peptide fragments of protein antigens presented to them by major histocompatibility complex class I molecules, human leukocyte antigen class I (HLA-I) in humans (Leone et al 2013)
Case group included 420 patients who were diagnosed with non-small cell lung carcinoma (NSCLC) at the No 1 and No 3 Affiliated Hospitals of Kunming Medical University (China)
We found here some associations of ERAP1 single nucleotide polymorphisms (SNPs) with prevalence of nonsmall cell lung carcinoma (NSCLC)
Summary
Eradication of tumor cells is mediated by CD8? cytotoxic T cells, which recognize peptide fragments of protein antigens presented to them by major histocompatibility complex class I molecules, human leukocyte antigen class I (HLA-I) in humans (Leone et al 2013). Cytotoxic T cells, which recognize peptide fragments of protein antigens presented to them by major histocompatibility complex class I molecules, human leukocyte antigen class I (HLA-I) in humans (Leone et al 2013). Peptides bound and presented by HLA-I molecules are prepared by antigen-processing S118. Immunoproteasome—a multiprotein complex in the cytosol—proteolytically cuts protein chains into peptides, which are transported to the endoplasmic reticulum by transporter associated with antigen processing molecules. The abnormalities of ERAP1 result in changes in HLA-I expression and impaired T cell responses. The aim of the current study was to evaluate the associations of four coding and nonsynonymous SNPs (rs26653G [ C [R127P], rs26618T [ C [I276 M], rs30187C [ T [K528R], rs27044C [ G [Q730E]) in the ERAP1 gene with NSCLC in two populations: Chinese Han and Polish Caucasians. The rationale behind comparison of these two populations was based on multiple differences described for Orientals and Caucasians in genetic associations with diseases (see ‘‘Discussion’’)
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