Association between HLA-G 3'UTR 14-bp ins/del polymorphism and susceptibility to breast cancer

Abstract

Human leukocyte antigen G (HLA-G) is a non-classic major histocompatibility complex (MHC) class I molecule that is highly expressed in cancer pathologies. A 14-bp insertion/deletion polymorphism in exon 8 of the 3' untranslated region (3'-UTR) of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. This study aimed to evaluate the association of 14-bp ins/del polymorphism in HLA-G gene and breast cancer in a south-east Iranian population. This study was performed using 236 patients with breast cancer and 203 healthy subjects. We designed a rapid and simple bi-directional PCR allele-specific amplification (Bi-PASA) for detection of 14-bp ins/del polymorphism in the HLA-G gene. The results of our study revealed that the prevalence of HLA-G 14-bp homozygote deletion genotype was higher in breast cancer patients than in the control group (OR=2.06, 95%CI=1.23-3.44, P=0.006). The frequency of the Del allele was 56.4% in breast cancer patients and 46.5% in the control group and the difference was statistically significant (OR=1.48, 95%CI=1.13-1.94, P=0.004). Moreover we evaluated the possible correlation of the HLA-G 14-bp ins/del genotypes and clinical characteristics of the patients, but no statistically significant correlation was found (P> 0.05). Our findings, for the first time, suggest that the 14-bp insertion/deletion polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to breast carcinoma. Further studies on larger populations with different ethnicities are required to verify our findings.

14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran

“…There is growing documents to support the viewpoint that some miRNA specifically regulate HLA-G expression by targeting its 3´UTR (Veit and Chies, 2009;Manaster et al, 2012). The 14 bp deletion allele has been associated with high expression of HLA-G mRNA, whereas The 14 bp Ins allele (5'-ATTTGTTCATGCCT-3') has been associated with low expression of HLA-G and low production of most mRNA isoforms (Hviid et al, 2004;Martelli et al, 2013;Jeong et al, 2014) The 14bp InDel polymorphism has been extensively studied in many different publications (Moon et al, 2011;Eskandari et al, 2013). In research on south-east Iranian population, suggest that the 14-bp InDel polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to breast carcinoma (Eskandari et al, 2013).…”

“…The 14 bp deletion allele has been associated with high expression of HLA-G mRNA, whereas The 14 bp Ins allele (5'-ATTTGTTCATGCCT-3') has been associated with low expression of HLA-G and low production of most mRNA isoforms (Hviid et al, 2004;Martelli et al, 2013;Jeong et al, 2014) The 14bp InDel polymorphism has been extensively studied in many different publications (Moon et al, 2011;Eskandari et al, 2013). In research on south-east Iranian population, suggest that the 14-bp InDel polymorphism in HLA-G gene could be a genetic risk factor for the susceptibility to breast carcinoma (Eskandari et al, 2013). The meta-analysis study suggested that HLA-G 14-bp InDel polymorphism might contribute to breast cancer susceptibility and overall cancer risk among Asians (Yz et al, 2014).…”

“…Several studies have shown that certain polymorphisms in HLA-G gene are associated with pregnancy complications such as preeclampsia and recurrent miscarriage (Wang et al, 2013;Enghelabifar et al, 2014) and cancer patient (Moon et al, 2011;Eskandari et al, 2013). The 14bp InDel polymorphism located in exon 8 of the 3' untranslated region (3' UTR) of the HLA-G gene was firstly reported in 1993 (Harrison et al, 1993).…”

Polymorphisms in HLA-DRB1 Gene and the Risk of Tuberculosis: A Meta-analysis of 31 Studies

“…T cells play a central role in immune protection which recruits neutrophils, eosinophils, and basophils to sites of infection and inflammation, to help B cells make antibodies, to induce macrophages to develop enhanced microbicidal activity, and through their production of cytokines and chemokines, to orchestrate the full panoply of immune responses [7]. Thereby, lot of studies demonstrated that there is close relationship between the HLA gene polymorphisms and infection disease, cancer, inflammatory, and autoimmune disease [8][9][10][11][12][13]. In addition, growing studies found that the HLA Class II gene, especially HLA-DRB1 gene polymorphisms, might significantly influence of TB risk [14][15][16], but the results have been inconclusive.…”

FEN1 −69G>A and +4150G>T polymorphisms and breast cancer risk

“…Genetic and environmental factors are involved in BC pathogenesis; however, its exact etiology is complicated and not clearly identified (5). A previous study demonstrated that genetic factors are important in the development of BC in populations in the southeast of Iran (6)(7)(8)(9)(10)(11).…”