The Toll-like Receptor 4 Polymorphism Asp299Gly Is Associated with an Increased Risk of Ovarian Cancer

Kania, Katarzyna; Haręża, Daria A.; Wilczyński, Jacek R.; Wilczyński, Miłosz; Jarych, Dariusz; Malinowski, Andrzej; Paradowska, Edyta

doi:10.3390/cells11193137

Cited by 8 publications

(6 citation statements)

References 80 publications

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“…They reported the highest frequency of heterozygous genotype and minor alleles of the polymorphism, which were AG and G, respectively. They concluded that the Asp299Gly variation could increase the risk of developing OC [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Association of Toll-Like Receptor 4 (TLR4) Gene Polymorphism (rs4986790) With Oral Squamous Cell Carcinoma (OSCC): A Pilot Case-Control Study

Gautam,

Pandi,

Girija

et al. 2024

Cureus

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Introduction Oral squamous cell carcinoma (OSCC) is a highly prevalent and most common form of oral malignancy in the Indian population. Toll-like receptors belong to an important family of receptors that are involved in the process of pathogen recognition and mounting immune response. The expression of this receptor is dysregulated on the tumor cells as reported across several cancer types. The genetic variants in this gene could have a profound impact on the expression of the Toll-like receptor 4 ( TLR4) gene. Objective This study aimed to understand the association of TLR4 gene polymorphism (rs4986790) with OSCC. The objective of this study was to compare the allele and genotype frequencies between the two groups, viz., OSCC and normal healthy subjects, recruited in the study. Materials and methods The blood samples were collected from normal healthy subjects (N = 25) and OSCC patients (N = 25). Genomic DNA was isolated from all samples, and genotyping was performed for the TLR4 gene polymorphism (rs4986790) employing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The frequency distribution of genotypes and alleles across the study groups was determined by the Chi-square test. Results The allele frequency for TLR4 gene polymorphism (rs4986790) in the case group was found to be 60% (A allele) and 40% (G allele), respectively. The study population in both groups were found to agree with the Hardy-Weinberg equilibrium (HWE). The genotype frequency did not differ significantly among the two study groups which was evident from the p-value = 0.8285. Conclusion The present study did not report any significant association of the TLR4 polymorphic marker rs4986790 with OSCC. Further investigations into the association of other polymorphic markers in the TLR4 gene, among the larger population of OSCC patients, could provide evidence of their association with OSCC.

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Section: Discussionmentioning

confidence: 99%

Genetic Association of Toll-Like Receptor 4 (TLR4) Gene Polymorphism (rs4986790) With Oral Squamous Cell Carcinoma (OSCC): A Pilot Case-Control Study

Gautam,

Pandi,

Girija

et al. 2024

Cureus

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“…Among the 70 women with ovarian cancer enrolled in the Poland study, the heterozygous variant and the recessive G allele of rs4986790 were more frequently found than in the 130 healthy individuals, indicating an increased risk of OC for its carriers. No difference in the distribution of rs4986791 between the cases and controls was observed [ 104 ]. A study conducted at the “Hippocratic” General Hospital of Athens, Greece, which included 261 breast cancer patients and 480 healthy individuals, showed that Gly carriers of rs4986790 (Asp/Gly & Gly/Gly genotype) and the Gly allele were more common among the breast cancer cases ( p = 0.0031 and p = 0.0061, respectively) [ 105 ].…”

Section: Discussionmentioning

confidence: 99%

Pathomorphological Manifestations and the Course of the Cervical Cancer Disease Determined by Variations in the TLR4 Gene

et al. 2023

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Cervical cancer (CC) is often associated with human papillomavirus (HPV). Chronic inflammation has been described as one of the triggers of cancer. The immune system fights diseases, including cancer. The genetic polymorphism of pathogen recognition receptors potentially influences the infectious process, development, and disease progression. Many candidate genes SNPs have been contradictory demonstrated to be associated with cervical cancer by association studies, GWAS. TLR4 gene activation can promote antitumor immunity. It can also result in immunosuppression and tumor growth. Our study aimed to investigate eight selected polymorphisms of the TLR4 gene (rs10759932, rs1927906, rs11536898, rs11536865, rs10983755, rs4986790, rs4986791, rs11536897) and to determine the impact of polymorphisms in genotypes and alleles on the pathomorphological characteristics and progression in a group of 172 cervical cancer subjects with stage I–IV. Genotyping was performed by RT-PCR assay. We detected that the CA genotype and A allele of rs11536898 were significantly more frequent in patients with metastases (p = 0.026; p = 0.008). The multivariate logistic regression analysis confirmed this link to be significant. The effect of rs10759932 and rs11536898 on progression-free survival (PFS) and overall survival (OS) has been identified as important. In univariate and multivariate Cox analyses, AA genotype of rs11536898 was a negative prognostic factor for PFS (p = 0.024; p = 0.057, respectively) and OS (p = 0.008; p = 0.042, respectively). Rs11536898 C allele predisposed for longer PFS (univariate and multivariate: p = 0.025; p = 0.048, respectively) and for better OS (univariate and multivariate: p = 0.010; p = 0.043). The worse prognostic factor of rs10759932 in a univariate and multivariate Cox analysis for survival was CC genotype: shorter PFS (p = 0.032) and increased risk of death (p = 0.048; p = 0.015, respectively). The T allele of rs10759932 increased longer PFS (univariate and multivariate: p = 0.048; p = 0.019, respectively) and longer OS (univariate and multivariate: p = 0.037; p = 0.009, respectively). Our study suggests that SNPs rs10759932 and rs11536898 may have the potential to be markers contributing to the assessment of the cervical cancer prognosis. Further studies, preferably with larger groups of different ethnic backgrounds, are needed to confirm the results of the current study.

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“…In ovarian cancer, high expression of TLR4 and MyD88 was found to predict poorer overall survival in patients with EOCs [98]. A polymorphism in TLR4 was also found recently to be associated with increased ovarian cancer risk [99]. Of note, TLR pathways have dichotomous roles in cancer development [100].…”

Section: Common Innate Immune Program In Lpsmentioning

confidence: 96%

Innate Immune Program in Formation of Tumor-Initiating Cells from Cells-of-Origin of Breast, Prostate, and Ovarian Cancers

Han

Chen

2023

Cancers

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Tumor-initiating cells (TICs), also known as cancer stem cells (CSCs), are cancer cells that can initiate a tumor, possess self-renewal capacity, and can contribute to tumor heterogeneity. TICs/CSCs are developed from their cells-of-origin. In breast, prostate, and ovarian cancers, progenitor cells for mammary alveolar cells, prostate luminal (secretory) cells, and fallopian tube secretory cells are the preferred cellular origins for their corresponding cancer types. These luminal progenitors (LPs) express common innate immune program (e.g., Toll-like receptor (TLR) signaling)-related genes. Microbes such as bacteria are now found in breast, prostate, and fallopian tube tissues and their corresponding cancer types, raising the possibility that their LPs may sense the presence of microbes and trigger their innate immune/TLR pathways, leading to an inflammatory microenvironment. Crosstalk between immune cells (e.g., macrophages) and affected epithelial cells (e.g., LPs) may eventually contribute to formation of TICs/CSCs from their corresponding LPs, in part via STAT3 and/or NFκB pathways. As such, TICs/CSCs can inherit expression of innate-immunity/TLR-pathway-related genes from their cells-of-origin; the innate immune program may also represent their unique vulnerability, which can be explored therapeutically (e.g., by enhancing immunotherapy via augmenting TLR signaling).

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The Toll-like Receptor 4 Polymorphism Asp299Gly Is Associated with an Increased Risk of Ovarian Cancer

Cited by 8 publications

References 80 publications

Genetic Association of Toll-Like Receptor 4 (TLR4) Gene Polymorphism (rs4986790) With Oral Squamous Cell Carcinoma (OSCC): A Pilot Case-Control Study

Genetic Association of Toll-Like Receptor 4 (TLR4) Gene Polymorphism (rs4986790) With Oral Squamous Cell Carcinoma (OSCC): A Pilot Case-Control Study

Pathomorphological Manifestations and the Course of the Cervical Cancer Disease Determined by Variations in the TLR4 Gene

Innate Immune Program in Formation of Tumor-Initiating Cells from Cells-of-Origin of Breast, Prostate, and Ovarian Cancers

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