Differences in genetic variation in antigen-processing machinery components and association with cervical carcinoma risk in two Indonesian populations

Abstract

Genetic variation of antigen-processing machinery (APM) components has been shown to be associated with cervical carcinoma risk and outcome in a genetically homogeneous Dutch population. However, the role of APM component single nucleotide polymorphisms (SNPs) in genetically heterogeneous populations with different distributions of human papillomavirus (HPV) subtypes remains unclear. Eleven non-synonymous, coding SNPs in the TAP1, TAP2, LMP2, LMP7 and ERAP1 genes were genotyped in cervical carcinoma patients and healthy controls from two distinct Indonesian populations (Balinese and Javanese). Individual genotype and allele distributions were investigated using single-marker analysis, and combined SNP effects were assessed by haplotype construction and haplotype interaction analysis. Allele distribution patterns in Bali and Java differed in relation to cervical carcinoma risk, with four ERAP1 SNPs and one TAP2 SNP in the Javanese population showing significant association with cervical carcinoma risk, while in the Balinese population, only one TAP2 SNP showed this association. Multimarker analysis demonstrated that in the Javanese patients, one specific haplotype, consisting of the ERAP1-575 locus on chromosome 5 and the TAP2-379 and TAP2-651 loci on chromosome 6, was significantly associated with cervical carcinoma risk (global P = 0.008); no significant haplotype associations were found in the Balinese population. These data indicate not only that genetic variation in APM component genes is associated with cervical carcinoma risk in Indonesia but also that the patterns of association differ depending on background genetic composition and possibly on differences in HPV type distribution.

Antigen processing and immune regulation in the response to tumours

“…Single nucleotide polymorphisms in ERAP1 have been associated with poorer prognosis and greater disease progression in human papillomavirus‐positive cervical carcinoma . A combination of SNP in ERAP1, TAP2 and LMP7 is associated with an increased risk of developing cervical carcinoma . In addition, the presence of a homozygous ERAP1 haplotype (ERAP1‐56 major and ERAP‐127 minor) correlates with a significantly worse overall survival, highlighting ERAP1 as an independent predictor of survival .…”

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

“…To date, over 30 genes have been studied for their role in cervical cancer risk and these include, Bid, BRIP1, Caspase 8, CCR2, CTLA4, CYP1A1, EXO1, FASLG, FASR, HOTAIR, IFN gamma, PARP1, XRCC1, MDM2, IL10, IL12, HLA B/C, MTHFR, Tap2, TNF-a, TLR9, p16, PIK3CA, p21, and p53 Martínez-Nava et al, 2016;Mehta et al, 2015;Mei et al, 2014;Dos Santos et al, 2016;Sousa et al, 2011;Tsakogiannis et al, 2017;and Wang et al, 2017). Of these, genes only nine have been researched in African populations, highlighting a big gap in cervical cancer molecular epidemiology studies in a continent where 90% of the cervical cancer-related deaths are predicted (MboubaBouassa et al, 2017).…”

“…Current reports show the involvement of Caspase 8, CCR2, CTLA4, CYP1A1, EXO1, FASLG, FASR, HOTAIR, IFN gamma, PARP1, XRCC1, MDM2, IL10, IL12, HLA B/C, MTHFR, Tap2, TNF-a, TLR9, p16, PIK3CA, and p21 in cervical susceptibility (Alanazi et al, 2013;Barbisan et al, 2012;Chang et al, 2015;Jin et al, 2017;Ma et al, 2013;Martínez-Nava et al, 2016;Mehta et al, 2015;Mei et al, 2014;Piccolo and Crispi, 2012;Roszack et al, 2014;Dos Santos et al, 2016;Sousa et al, 2011;Tsakogiannis et al, 2017;Wang et al, 2017;and Zhuo et al, 2014). However, these findings have mostly been corroborated in Caucasian and Asian populations, and only a few have been reported on African populations.…”

An Overview on ERAP Roles in Infectious Diseases

“…To further investigate the contribution of genetic variations in the APM to HPV-induced cervical carcinoma risk, A.M Mehta et al in 2015 conducted a further study on the genotype and genotype interactions of 11 previously identified SNPs in seven genes coding for some APM components, including ERAP1 [86]. The analysis was based on the occurrence of these variants in Javanese and Balinese Indonesian populations, in whom HPV is almost endemic [87].…”