The Impact of <i>HLA-G</i> 3′UTR Polymorphisms in Breast Cancer in a Tunisian Population

Ouni, Nesrine; Chaaben, Arij Ben; Kablouti, Ghalia; Ayari, Fayza; Douik, Hayet; Abaza, Hajer; Gara, Sonia; Elgaaied-Benammar, Amel; Guémira, Fethi; Tamouza, Ryad

doi:10.1080/08820139.2019.1569043

Cited by 24 publications

(17 citation statements)

References 52 publications

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“…Concerning the allelic frequency, also no significant difference was found between the patients and control groups at HLA-G 14bp ins/del (22) . The present results were disagree with AL-Omar and Mansour (23) who showed a high significant increase between the 14-bp del allele and occurrence of breast cancer, also our results disagree with the Tunisian results which confirmed the elevation of deletion allele frequencies among the patients in comparison with the control group and conferred a risk to breast cancer development (52% Vs 45%) (24) . These discrepancies in the results may be associated with the genetic variations between various ethnic people investigated, geographic climate, daily lifestyle, ethnic diversity and dietary habits (8) .…”

Section: Discussioncontrasting

confidence: 99%

HLA-G 14-bp Insertion /Deletion (In/Del) Polymorphism in Breast Cancer Iraqi Arabian women

Salman,

Mahood,

Al-Abassi

2021

Indian Journal of Forensic Medicine & Toxicology

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Background: Breast cancer is a group of diseases in which the breast cells change and divide uncontrolled, typically resulting in a lump or mass. Human leukocyte antigen -G (HLA-G) gene is a none -classic major histocompatibility complex (MHC) class I molecule that is highly expressed in cancer pathologies and is one of the strategies used by tumor cells to escape immune surveillance. A14-bp insertion/deletion (In/Del) 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. The present study aimed to the genotyping of the 14-bp In/Del in the HLA-G gene and its relation with clinical characteristics in Iraqi Arab breast cancer women.Materials and methods : Sixty women affected with breast cancer were enrolled in this study, in addition to 40 age -sex and ethnically matched healthy individuals participated as the control group, genotyping was performed using conventional polymerase chain reaction (PCR) and electrophoresis assays with specific primers. Results:The results of current study revealed that the prevalence of HLA-G 14-bp homozygous insertion genotype (ins/ins) was higher in breast cancer patients (26.7%) , while in control group (12.5%) ( OR = 2.55, 95%CI=0.86-7.54 , P= 0.088). The frequency of the ins allele was higher in breast cancer patients (51.7%), while in the control group (40 %), but no significant differences were observed in the distribution of alleles and genotypes between the patients and control groups. Moreover, we evaluated the possible correlation of the HLA-G 14-bp In/Del genotypes and clinical characteristics of the patients, but no statistically significant correlation was found, except for histologic grade and tumor type under (P≤ 0.05). Conclusion:The result revealed the most frequencies polymorphism is the homozygous insertion genotype (ins/ins) of the HLA-G 14-bp and its allele in Iraqi Arabian breast cancer women. No significant association between this polymorphic site and breast cancer although the data revealed a significant relation in genotype and allele frequency of 14-bp polymorphism between grade I, II, and III of breast cancer patients Larger case-control study including other polymorphic sites of the HLA-G gene is necessary to substantiate the importance of HLA-G polymorphisms and linkage disequilibrium in breast cancer risk.

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Section: Discussioncontrasting

confidence: 99%

HLA-G 14-bp Insertion /Deletion (In/Del) Polymorphism in Breast Cancer Iraqi Arabian women

Salman,

Mahood,

Al-Abassi

2021

Indian Journal of Forensic Medicine & Toxicology

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“…Breast cancer is a multifactorial disease caused by multiple genetic factors with possible contributions or interactions with environmental factors. Our previous case-control studies on immune-related anti-tumour responses showed that non-classical human leucocyte antigen molecules HLA-G, HLA-E and MICA are associated with breast cancer risk (Ouni et al, 2019(Ouni et al, , 2017.…”

Section: Discussionmentioning

confidence: 99%

MICA‐129 Met/Val polymorphism could be a genetic biomarker for Familial Breast Cancer in the Tunisian population

Ouni

Chaaben

Ayari

et al. 2020

Int J Immunogenetics

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Identification of candidate genes associated with susceptibility of breast cancer can have a significant impact at a cancer management national healthcare systems level, making genetic testing more affordable and cost‐effective. We have previously shown that the major histocompatibility complex class I‐related chain A (MICA) was related to breast cancer and plays an important role in modulating immune response mechanisms through NKG2D receptor activation. Compared to our previous study, in this work, we recruited a new cohort composed of 354 unrelated Tunisian women affected by breast cancer and 380 age‐matched women as controls, all genotyped for MICA‐129 Met/Val (rs 1051792). Subsequently, we exanimated the distribution of this polymorphism in ten families. As a result, an association was found between the Val allele and Val/Val genotype and the risk of breast cancer (p = 2.5 × 10–15; OR = 2.40; p = 6.5 × 10–13; OR = 3.03, respectively). Stratified analysis with age and family history of cancer revealed an association between the Val/Val genotype and younger patients <40 years (p = .003; OR = 2.03). Among those patients having a family history of cancer, 68% had a Val/Val genotype (p = .02; OR = 1.82). In the family study, an analyse of pedigrees revealed that the majority of families showed the development of breast cancer at a young age. Moreover, all patients diagnosed with early‐onset breast cancer had a Val/Val genotype. Our results lead us to propose that this polymorphism may be an inherited genetic biomarker contributing to an increased breast cancer risk in Tunisian women.

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“…The mRNA stability of HLA-G was found associated with a 14-bp insertion/deletion in exon 8 of the 3' untranslated region. A series of studies have shown that HLA-G polymorphism could be a diagnostic and prognostic marker for the susceptibility and pathogenesis of breast cancer in populations from different regions (53)(54)(55)(56)(57)(58)(59). MicroRNAs were also found to be involved in the regulation of HLA-G expression in breast cancer.…”

Section: Hla-g/kir2dl4 Expression In Breast Cancer Immune Microenviro...mentioning

confidence: 99%

Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment

2022

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Human leukocyte antigen (HLA)-G is a nonclassical MHC Class I molecule, which was initially reported as a mediator of immune tolerance when expressed in extravillous trophoblast cells at the maternal-fetal interface. HLA-G is the only known ligand of killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4), an atypical family molecule that is widely expressed on the surface of NK cells. Unlike other KIR receptors, KIR2DL4 contains both an arginine–tyrosine activation motif in its transmembrane region and an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail, suggesting that KIR2DL4 may function as an activating or inhibitory receptor. The immunosuppressive microenvironment exemplified by a rewired cytokine network and upregulated immune checkpoint proteins is a hallmark of advanced and therapy-refractory tumors. Accumulating evidence has shown that HLA-G is an immune checkpoint molecule with specific relevance in cancer immune escape, although the role of HLA-G/KIR2DL4 in antitumor immunity is still uncharacterized. Our previous study had shown that HLA-G was a pivotal mediator of breast cancer resistance to trastuzumab, and blockade of the HLA-G/KIR2DL4 interaction can resensitize breast cancer to trastuzumab treatment. In this review, we aim to summarize and discuss the role of HLA-G/KIR2DL4 in the immune microenvironment of breast cancer. A better understanding of HLA-G is beneficial to identifying novel biomarker(s) for breast cancer, which is important for precision diagnosis and prognostic assessment. In addition, it is also necessary to unravel the mechanisms underlying HLA-G/KIR2DL4 regulation of the immune microenvironment in breast cancer, hopefully providing a rationale for combined HLA-G and immune checkpoints targeting for the effective treatment of breast cancer.

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The Impact of HLA-G 3′UTR Polymorphisms in Breast Cancer in a Tunisian Population

Cited by 24 publications

References 52 publications

HLA-G 14-bp Insertion /Deletion (In/Del) Polymorphism in Breast Cancer Iraqi Arabian women

HLA-G 14-bp Insertion /Deletion (In/Del) Polymorphism in Breast Cancer Iraqi Arabian women

MICA‐129 Met/Val polymorphism could be a genetic biomarker for Familial Breast Cancer in the Tunisian population

Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment

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