Genetic variation of antigen processing machinery components and association with cervical carcinoma

Abstract

The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of several APM components is associated with progression and clinical outcome in cervical carcinoma. Genetic variation in the genes encoding APM components is known to be associated with risk of occurrence of several malignancies. However, only limited evidence exists supporting the role of single nucleotide polymorphisms (SNPs) in APM components in cervical carcinoma. We have therefore investigated the occurrence of APM component SNP genotypes and haplotypes in cervical carcinoma. Thirteen coding SNPs in the LMP2, LMP7, TAP1, TAP2, and ERAP1 genes were genotyped in 127 cervical carcinoma patients and 124 controls. Individual genotype and allele distributions were assessed by single-marker analysis. Effects of various SNP combinations were estimated by haplotype construction and subsequent haplotype interaction analysis. Significant haplotypes were modeled on disease risk. Allele distributions at the LMP7-145, TAP2-651, ERAP1-127, and ERAP1-730 loci differed significantly between cases and controls with the major allele at the LMP7 and TAP2 loci and the minor allele at both ERAP1 loci associated with increased cervical carcinoma risk. A combination of the two haplotypes spanning these loci was associated with a three-fold increased risk (OR = 3.024; P << 0.001); approximately 12% of all cervical carcinoma occurrences were attributable to this combination. Our data indicate that combined genetic variation in the TAP2, LMP7, and ERAP1 genes is associated with increased cervical carcinoma risk.

Low Molecular Mass Polypeptide and Transporter Antigen Peptide Genes Polymorphism as the Risk Factors of Cervical Cancer Which Caused by Human Papillomavirus Type-16 Infection in Bali

“…7,10 A study in Netherlands that was similar with our study showed that the decreasing expression of TAP-1 did not having correlation with the survival rate cervical cancer patients. 11 In the study that was conducted to know the expression of TAP-1 and LMP-2 upon mice, found that the tumor incidence was not different from the control group. Even though LMP and TAP was already confirmed to play a role in detecting and presenting antigen towards HLA, but the specific role of each LMP-2, LMP-7, TAP-1 and TAP-2 genes had not been known yet due to inadequate study before.…”

“…In this study also suggested that LMP-7 and TAP-2 genes polymorphisms was correlated with the progress of the disease. 11 That study was not investigating the correlation with HPV-16 specifically.…”

Association of TAP1 and TAP2 Gene Polymorphisms with Hematological Malignancies

“…Polymorphisms of TAP genes have been associated with various diseases such as tuberculosis (Wang et al, 2012), ankylosing spondylitis (Feng et al, 2009), leprosy (Shinde et al, 2013), idiopathic bronchiectasis (Dogru et al, 2007), cystic fibrosis (Ozbas-Gerceker et al, 2002) and also with the risk of occurence of several malignant tumors including colon cancer (Yang et al, 2005), cervical carcinoma (Mehta et al, 2007) and esophageal carcinoma (Cao et al, 2005). To the best of our knowledge there has been no study on the association of TAP gene polymorphisms with hematological malignancies.…”

“…TAP gene polymorphisms were found to be associated with colon cancer (Yang et al, 2005), cervical carcinoma (Mehta et al, 2007) and esophageal carcinoma (Cao et al, 2005). However, literature rewieving yielded no specific study on the role of TAP polymorphisms in the pathogenesis of hematological malignancies.…”

Survival of the fittest or best adapted: HLA-dependent tumor development

“…Furthermore, in some malignancies the frequency of HLA class I APM downregulation is associated with higher grading, staging, aggressive histology and abnormal DNA content of tumors, which is often more pronounced in metastases when compared to primary lesions and associated with a reduced patients' survival. [52][53][54][55][56][57] Matsushita et al 58 found that a strong HLA-DR-positive expression on colorectal cancer cells was significantly related to better prognosis for the cancer patients. They have also suggested a possible role for c-myc and propose that HLA DR is up-regulated while c-myc is suppressed by interferon gamma (IFN-γ), thus decreasing levels of c-myc in cancer tissue with high levels of IFN-γ.…”