Association of HLA-G +3142 C>G polymorphism and breast cancer in Tunisian population

Abstract

HLA-G is highly expressed in cancer. Also, it is associated to its progression. Here, we explored the relationship between two HLA-G polymorphisms with breast cancer (BC) and tried to make a correlation with sHLA-G levels. We genotyped 104 patients with BC and 83 controls (CTRL) for HLA-G 14-bp insertion/deletion (Ins/Del) and HLA-G +3142 C>G polymorphisms. The mutations were identified with PCR and PCR-RFLP. The sHLA-G dosage was performed on plasma samples by a specific ELISA. A significant association with BC was found concerning the G allele in the +3142 C>G polymorphism (p = 0.0004). The G/G genotype is the protective genotype (1 % in BC patients vs. 13.1 % in CTRL, OR 0.065, 95 % CI 0.008-0.523). No statistically significant differences were observed for the 14-bp Ins/Del polymorphism between BC patients and controls frequencies. The protection by G/G genotype of +3142 C>G polymorphism is maintained in young patients (<50 years, p = 0.0006) and in early-diagnosed BC patients (<50 years, p = 0.0033). In addition, an association was found between the haplotypes inferred by both HLA-G polymorphisms and BC susceptibility. Indeed, the (DelG) haplotype is found as the protective haplotype against BC (OR 0.269, 95 % CI 0.081-0.895, p = 0.023). The ELISA dosage of sHLA-G revealed increased levels in BC compared to CTRL (p < 0.0001). We demonstrated also that sHLA-G is closely associated with advanced stages of BC without significance. sHLA-G is increased in TNM IV and SBR III subgroups. It is also enhanced in patients with a tumor size over 20 mm and in triple-negative patients. Taken together, our findings demonstrate, for the first time, the association of HLA-G +3142 C>G polymorphism with BC susceptibility in Tunisian population. Our results revealed also a potential implication of sHLA-G in advanced stages of BC.

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

“…Interestingly, the wild-type ins/ins genotype was absent among Saudi patients, suggesting that the ins allele has a highly protective effect. 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).…”

“…Different results have also been reported regarding the association between the level of expression of HLA-G molecule and BC. While the majority of these studies have reported increased levels of HLA-G in patients (Chen et al, 2010;Eskandari-Nasab et al, 2013;Jeong et al, 2014;Ramos et al, 2014;Zidi et al, 2016), a few studies, however, did not find differences between patients and controls (Palmisano et al, 2002). A recent meta-analysis revealed that the HLA-G 14-bp ins/del polymorphism may contribute to BC susceptibility and overall cancer risk in Asian populations (Ge et al, 2014).…”

“…The HLA-G molecule was reported for its tolerogenic function mainly in the maternal-fetal interface, helping to protect the fetus from destruction by the mother's immune defense system (Kovats et al, 1990;Menter and Tzankov, 2018;Galaviz-Hernandez et al, 2019). Considering the tolerogenic properties of the HLA-G molecule, many studies have detected an association between the aberrant expression of HLA-G and the occurrence of several types of malignancies such as colorectal cancer, esophageal cancer, uterine cervical cancer, ovarian carcinoma, hepatocellular carcinoma, carcinoma of bladder, and breast cancer (Rouas-Freiss et al, 2005a;Zidi and Ben Amor, 2011;Kim et al, 2013;Rolfsen et al, 2014;Rutten et al, 2014;Zhang and Tao Wang, 2014;Zidi et al, 2016;Zambra et al, 2016;de Almeida et al, 2018;Lin and Yan, 2018) as well as several other diseases such as infections, autoimmunity, and abortion (Donadi et al, 2011;Vargas et al, 2011;Garcia et al, 2013;Dias et al, 2015;Sabbagh et al, 2018;). Different polymorphisms located in coding and noncoding regions of the gene were reported to affect the biological activity of HLA-G. Polymorphism in the promoter or 3′-UTR influence HLA-G levels.…”

Association ofHLA-G3'UTR 14-bp Ins/Del polymorphism with breast cancer among South Indian women

“…The meta-analysis study on cancer risk reported significant association of 14-bp Ins/Del polymorphism with breast cancer 29. In the Tunisian population,30 there is no association of 14-bp Ins/Del polymorphism with breast cancer. Though the 14-bp Ins/Del polymorphism is not associated with breast cancer predisposition in Brazilian31 and Iranian-Azeri32 populations, it has been shown to contribute to shorter survival time and disease progression, respectively.…”

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]…”