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

Abstract

Background: The human leukocyte antigen-G (HLA-G) gene is highly expressed in cancer pathologies and is one strategy used by tumor cells to escape immune surveillance. A 14-bp insertion/deletion (InDel) polymorphism of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. The aim of present study was to assess any genetic association between this polymorphism and breast cancer among Iranian-Azeri women. Materials and Methods: In this study 227 women affected with breast cancer, in addition to 255 age-sex and ethnically matched healthy individuals as the control group, participated. Genotyping was performed using polymerase chain reaction and electrophoresis assays. The data were compiled according to the genotype and allele frequencies, compared using the Chi-square test. Statistical significance was set at P<0.05. Results: In this case-control study, no significant difference was found between the case and control groups at allelic and genotype levels, although there is a slightly higher allele frequency of HLA-G 14bp deletion in breast cancer affected group. However,when the stage I subgroup was compared with stage II plus stage III subgroup of affected breast cancer, a significant difference was seen with the 14 bp deletion allele frequency. The stage II-III subgroup patients had higher frequency of deletion allele (57.4% vs 45.8%) than stage I cases (χ2=4.16, p-value=0.041). Conclusions: Our data support a possible action of HLA-G 14bp InDel polymorphism as a potential genetic risk factor for progression of breast cancer. This finding highlights the necessity of future studies of this gene to establish the exact role of HLA-G in progression steps of breast cancer.

Research Article Association of HLA-G 14-base pair insertion/deletion polymorphism with breast cancer in Saudi Arabia

“…However, in other studies, no associations were found in a group of women from northern Tunisia (Zidi et al, 2016). This was also observed in a South Korean population (Jeong et al, 2014) and Azeri population located in northwestern Iran (Haghi et al, 2015). In the latter study, a significant positive association was found between the del allele and advanced stages of BC (stage I vs stages II and III).…”

Genetic association between HLA-G 14-bp polymorphism and diseases: A systematic review and meta-analysis

“…Articles included comprised case-control studies involving the HLA-G 3′UTR 14-bp polymorphism and clinical situations/ diseases. Studies were grouped according to clinical characteristics, pathogenesis and immune response as follow: (1) cancer 2 -B-Cell Lymphoma [27], Breast Cancer [28][29][30][31][32], Cervical Cancer [33][34][35][36], Colorectal cancer [37], Esophageal Cancer [38], Hepatocellular Carcinoma [39][40][41], Head and Neck Squamous-Cell Carcinoma (HNSCC) [42], Lung Cancer [43], Neuroblastoma [44], Papillary Thyroid Cancer [45] and Prostate Cancer [46]; (2) autoimmune diseases 3 -Hashimoto's Thyroiditis [45], Juvenile Idiopathic Arthritis [47], Multiple Sclerosis [48][49][50][51], Non-segmental Vitiligo [52], Pemphigus Vulgaris [53], Rheumatoid Arthritis [47,[54][55][56][57][58], Systemic Lupus Erythematosus (LES) [59][60][61][62][63][64][65][66][67] and Type 1 Diabetes [68]…”

Mechanism of immune evasion in breast cancer

“…Expression levels of HLA-G increase in BC,21 which associates with poor prognosis 22. Following studies on a 14 bp InDel polymorphism in the HLA-G gene, Haghi et al performed genotyping and found that patients with higher BC stages had a higher frequency of allele deletion compared with patients with lower stages, indicating that the 14 bp InDel polymorphism in the HLA-G gene was a risk factor for the development of BC 23. In addition, the area under the curve for receiver operating characteristic values of the soluble form of HLA-G (sHLA-G) can help identify metastasis, suggesting that sHLA-G may be utilized as a biomarker for the diagnosis of BC, particularly at the metastasis stage 24.…”