Study On The Association Of ERAP Genetic Polymorphisms With Non-Small Cell Lung Cancer

Background Lung cancer,the most common malignant tumor, which is a serious threat to human health,and the incidence and mortality of lung cancer has shown a rising trend in the worldwide. Non-small cell lung cancer accounted for about 80% of lung cancer. Polypeptides of endogenous antigen produced by antigen processing serve as T lymphocyte (CTL) epitopes presented by major histocompatibility complex (MHC) class I molecules,which play a critical role in the anti-tumor immune responses. Endoplasmic reticulum aminopeptidase 1 (ERAP1) and the closely related ERAP2 are involved in the final trimming of peptides within the endoplasmic reticulum for presentation by MHC class I molecules. ERAP genetic polymorphism influences antigen presenting and causes different immune response, eventually leading to the different occurrence and prognosis of disease. Now most of the studies concentrate on the association between the genetic polymorphism of ERAP1 and the pathogenesis of autoimmune disorder such like ankylosing spondylitis, meanwhile, the reports about ERAP2 genes with disease are very few. The main purpose of this study is to evaluate the association between the genetic polymorphisms of ERAP and the susceptibility of NSCLC, and it helps to understand the role of MHC class I antigen-presenting gene system in the anti-tumor immunity.Methods A total of 342 NSCLC patients and 324 matched healthy controls in Yunnan Han population was collected in present study. Using TaqMan fluorescence probe technique, the SNPs of rs27044,rs30187,rs26618,rs26653 in ERAP1 gene,and the SNPs of rs2248374, rs2549782 in ERAP2 gene were genotyped, and constructed their haplotypes. Then, the association between these SNPs with NSCLC was assessed.Results ① The genotype distribution of six SNPs in NSCLC and healthy control groups were according to Hardy-Weinberg balance;② the genotypic and allelic frequencies of the SNPs of rs27044,rs30187,rs26618,rs26653 in ERAP1 gene showed significant difference between NSCLC patients and the control groups (P<0.05);The frequencies of haplotype rs27044/rs30187/rs26618/rs26653-CCCG,GCTC,GTTC also showed difference between NSCLC patients and the control groups (P<0.05);③The allelic frequency of rs2248374,the genotypic and allelic frequencies of rs2549782 showed significant difference between NSCLC patients and the control groups (P< 0.05);The frequencies of haplotype rs2248374/rs2549782-AG and GT also showed difference between NSCLC patients and the control groups (P<0.05);④The genotypes and allelic frequencies of the SNPs of rs27044,rs30187,rs26618,rs26653 in ERAP1 gene had no statistical significance in patients of adenocarcinoma and squamous cell carcinoma, and also in the Phase I+II NSCLC and the Phase III+IV NSCLC patients (P>0.05);⑤The allelic frequencies of the SNPs of rs2248374,rs2549782 in ERAP2 gene had statistical significance in patients of adenocarcinoma and squamous cell carcinoma(P <0.05),but in the Phase I+II NSCLC and the Phase III+IV NSCLC patients,there was no statistical significance.Conclusions ERAP gene polymorphisms were associated with the susceptibility of NSCLC. In details, the of haplotype rs27044/rs30187/rs26618/rs26653-CCCG,GCTC was likely to increase the risk of NSCLC, the haplotype of rs27044/rs30187/rs26618/ rs26653-GTTC was likely to exert a protective role on NSCLC, and the haplotype of rs2248374/rs2549782-AG was likely to increase the risk of NSCLC, the haplotype of rs2248374/rs2549782-GT was likely to exert a protective role on NSCLC. Additionally, the SNPs of rs2248374, rs2549782 in ERAP2 gene were associated with the pathological pattern of NSCLC.