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

Abstract

AimHuman leucocyte antigen-G (HLA-G) and tumour necrosis factor-alpha (TNF-α) are potent immune mediators implicated in the pathogenesis of breast cancer. The polymorphisms in the 3' untranslated region (3'UTR) of HLA-G and promoter region of TNF-α are well known to influence their expression levels and may consequently contribute to varied disease predisposition. Therefore, in the present study, we explored the effect of HLA-G 3'UTR (14-bp Ins/Del and +3142 C/G) and TNF-α promoter (–238 G/A and –308 G/A) polymorphisms on breast cancer risk among South Indian women.MethodsA total of 342 women (100 patients with breast cancer, 142 patients with benign breast disorder and 100 healthy women volunteers) were enrolled for this study. Genotyping of HLA-G and TNF-α polymorphisms were performed by direct PCR DNA amplification and amplification refractory mutation system PCR methods, respectively.ResultsSignificantly higher frequencies of HLA-G 14-bp Ins allele and Ins/+3142G haplotype were observed in patients with breast cancer than healthy controls (OR=1.56, Pc=0.036) and patients with benign breast disorder (OR=1.47, Pc=0.046). Similarly, subgroup analysis based on age at diagnosis (age≤50 years and >50 years) of breast cancer revealed higher frequencies of 14-bp Ins allele and Ins/+3142G haplotype in the patients of age >50 years than healthy controls (OR=1.77, Pc=0.03). Additionally, the extended haplotypes and multifactor dimensionality reduction analysis of the studied polymorphisms revealed significant contribution of HLA-G 14-bp Ins/Del polymorphism towards breast cancer risk.ConclusionThe findings of the present study suggest that the HLA-G 14-bp Ins/Del polymorphism could influence breast cancer pathogenesis among South Indian women.

Human leucocyte antigen – G gene polymorphism in laryngeal squamous cell carcinoma patients in Mansoura University Hospitals

“…The −14/-14 and −14/+14 genotypes had higher risk association with LSCC by 8.66 & 6.98 folds, respectively. In line with some previous studies, the risk of the esophageal carcinoma increases more in 14-bp del/del individuals than 14-bp ins/ins individuals by 2.69-fold [21,24,39].…”

Elevated sHLA-G plasma levels post chemotherapy combined with ILT-2 rs10416697C allele status of the sHLA-G-related receptor predict poorest disease outcome in early triple-negative breast cancer patients

“…Here, targeting the HLA-G-ILT2 ligand-receptor axis seems to be a promising tool for the immunotherapeutic intervention in TNBC patients. In preclinical trials, blocking the IC HLA-G-ILT2 ligand-receptor-axis by a first-in human ILT2 blocking antibody (BND-22) has shown efficient antitumor activity ( 52 ). Recently, a phase 1/2 trial in advanced or metastatic solid tumors, including them non-small cell lung cancer, cervical, colorectal and BC, evaluates NGM707, a novel dual antagonist antibody that inhibits the ILT2 and ILT4, as a monotherapy or in combination with Pembrolizumab (ClinicalTrials.gov Identifier: NCT04913337).…”

HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico

“…Our results are similar to the findings in South Indian women, in which the Ins allele is proposed as an important factor in the pathogenesis of BC. Nevertheless, they lacked an analysis of clinical variables [ 18 ]. Contrary to our findings, in populations from Tunisia and Iran, the Del allele is proposed as a risk factor for developing BC [ 19 , 32 , 33 , 34 ].…”

“…Nevertheless, the role of HLA-G SNVs in BC has already been suggested based on their biological interactions, although their precise mechanisms of action remain unclear [ 17 ]. In this respect, the HLA-G gene rs66554220 variant has been studied in different populations, with discordant results regarding its association with BC [ 15 , 18 , 19 ]. In Mexican people, however, there are no published studies on its association with cancer.…”