title: Single Nucleotide Polymorphisms of the ERAP1 Gene and Risk of NSCLC: A Comparison of Genetically Distant Populations, Chinese and Caucasian.
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.
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Disease, Institute of Medical Biology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Kunming, Yunnan, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiśniewski
authors.affiliation: Department of Thoracic Surgery, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Qiangli
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department and Clinic of Pulmonology and Lung Cancer, Wrocław Medical University, Wrocław, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Kowal
authors.affiliation: Department and Clinic of Pulmonology and Lung Cancer, Wrocław Medical University, Wrocław, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Porębska
authors.affiliation: Department and Clinic of Thoracic Surgery, Wrocław Medical University, Wrocław, Poland.
authors.forename: Konrad
authors.initials: K
authors.lastname: Pawełczyk
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Disease, Institute of Medical Biology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Kunming, Yunnan, China.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wrocław, Wrocław, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Dubis
authors.affiliation: Research and Development Centre, Regional Specialist Hospital in Wrocław, Wrocław, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Żuk
authors.affiliation: Department of Geriatrics, The No. 1 Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China.
authors.forename: Yingfu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Disease, Institute of Medical Biology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Kunming, Yunnan, China. shili.imb@gmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. pkusnier@iitd.pan.wroc.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuśnierczyk
mesh_terms: D000328:Adult; D000368:Aged; D000626:Aminopeptidases / Q000235:genetics*; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D002681:China; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People
chemical_list: D006680:HLA Antigens; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human
keywords: Endoplasmic reticulum aminopeptidase-1; Genetic association; Non-small cell lung carcinoma