RGD Reference Report - Single nucleotide polymorphisms in antigen processing machinery component ERAP1 significantly associate with clinical outcome in cervical carcinoma. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Single nucleotide polymorphisms in antigen processing machinery component ERAP1 significantly associate with clinical outcome in cervical carcinoma.

Authors: Mehta, AM  Jordanova, ES  Corver, WE  Van Wezel, T  Uh, HW  Kenter, GG  Jan Fleuren, G 
Citation: Mehta AM, etal., Genes Chromosomes Cancer. 2009 May;48(5):410-8.
RGD ID: 2315691
Pubmed: PMID:19202550   (View Abstract at PubMed)
DOI: DOI:10.1002/gcc.20648   (Journal Full-text)

Genetic variation of the antigen processing machinery (APM) components TAP2, LMP7, and ERAP1 is related to cervical carcinoma risk, although the relation with expression and clinical outcome remains unknown. We have investigated the occurrence of APM component single nucleotide polymorphisms (SNPs) in cervical carcinoma. Twelve nonsynonymous, coding SNPs in the TAP1, TAP2, LMP2, LMP7, and ERAP1 genes were genotyped in 75 cervical carcinoma patients with known APM component and HLA class I expression levels. Individual genotype distributions were assessed for association with APM component expression, various histopathological parameters and survival. Genotype distributions at the ERAP1-56 and ERAP1-127 loci were significantly associated with overall survival (OS); haplotype construction spanning these two SNPs revealed that the combination of a major allele at ERAP1-56 and a minor allele at ERAP1-127 was significantly associated with survival, homozygosity for this haplotype being associated with decreased OS (5-year survival 50% vs. 70 and 81% for complete absence or heterozygosity for this haplotype, respectively; P = 0.021). Heterozygosity for this haplotype was an independent predictor for better OS in multivariate analysis (HR = 0.219; P = 0.014). These data indicate that genetic variation in APM component genes, particularly ERAP1, is an important contributing factor in cervical carcinogenesis, progressive tumor growth and survival. The location of the ERAP1-127 SNP in the peptidase M1 domain of the ERAP1 aminopeptidase suggests the possibility of direct functional consequences of variation at this locus.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cervix carcinoma  IAGP 2315691; 2315691DNA:SNPs (human)RGD 
cervix carcinoma  ISOERAP1 (Homo sapiens)2315691; 2315691DNA:SNPs (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Erap1  (endoplasmic reticulum aminopeptidase 1)

Genes (Mus musculus)
Erap1  (endoplasmic reticulum aminopeptidase 1)

Genes (Homo sapiens)
APEX1  (apurinic/apyrimidinic endodeoxyribonuclease 1)
ERAP1  (endoplasmic reticulum aminopeptidase 1)


Additional Information