Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile in ovarian cancers

Wang, Ancong; Wu, Fengxia; Gao, Yongsheng; Sheng, Xiugui

doi:10.3892/ol.2014.2113

Cited by 9 publications

(5 citation statements)

References 22 publications

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“…The TLR4 Asp299Gly and Thr399Ile alleles were not detected in the 105 ovarian cancer patients in a study conducted in northern China. These results indicate that the TLR4 299Gly and 399Ile alleles were exhibited at a lower frequency in northern Chinese ovarian cancer patients compared to other studies [103]. 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.…”

Section: Discussionmentioning

confidence: 52%

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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Section: Discussionmentioning

confidence: 52%

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

et al. 2023

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“…Moreover, the TLR4 Asp299Gly polymorphism was detected in 15.0% (6/40) of women with HGSOC. The distribution of Asp299Gly and Thr399Ile was earlier analyzed in 105 Chinese women with OC, but these polymorphisms were not detected in the studied populations [75]. Several studies have confirmed the absence of rs4986790 in the Chinese population and a low prevalence of this SNP in Asian populations [39].…”

Section: Discussionmentioning

confidence: 91%

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

Kania

Haręża

Wilczyński

et al. 2022

Cells

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Ovarian cancer (OC) is one of the most common cancers threatening women’s lives around the world. Epithelial ovarian tumors represent the most common ovarian neoplasms. Most OC patients are diagnosed at the advanced stage, and there is an urgent need to identify novel biomarkers of the disease. Single-nucleotide polymorphisms (SNPs) in TLR genes may serve as crucial markers of cancer susceptibility. We investigated the frequency of TLR polymorphisms in a group of 200 women, including 70 with OC. Four SNPs, two each in TLR4 (rs4986790 and rs4986791) and TLR9 (rs187084 and rs5743836), were analyzed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The digested fragments were separated and identified by multicapillary electrophoresis. The load quantification of human papillomavirus (HPV) types 16/18 was determined using a digital droplet PCR method. We found an increased frequency of heterozygous genotype and minor allele of the TLR4 rs4986790 SNP in women with OC compared with healthy controls, and this result remained highly significant after Bonferroni’s correction for multiple testing (p < 0.0001). No evidence of linkage disequilibrium was found with any of the examined TLR SNPs. The findings suggest that the TLR4 Asp299Gly polymorphism could be a genetic risk factor for the development of OC.

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“…(rs4986791) in the Chinese population. They found that in ovarian cancer patients, rs4986790 and rs4986791 presented at a lower incidence [58]. Related to gastric cancer, a meta-analysis done by Zhou et al demonstrated that TLR4 + 896AA/G and + 1196C/T polymorphisms may be associated with significantly increased gastric cancer risk among the Caucasian population [59].…”

Section: • Potential Association Between Tlr4 Polymorphisms and Cancementioning

confidence: 99%

Toll-Like Receptors Gene Polymorphism and Susceptibility to Cancer Development

Semlali¹,

Alnemari²,

Almalki³

et al. 2018

Genetic Diversity and Disease Susceptibility

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Toll-like receptors (TLRs) play an important role in immune-surveillance and responses towards pathogenic and non-pathogenic microorganisms. They act as innate immune sensors against endogenous and exogenous danger signals by recognizing the pattern recognition molecules (DAMPs and PAMPs) and drive an adaptive immune response through their signaling pathways, which leads to NF-κB and IRF3 transactivation and induces different inflammatory cytokine genes. TLRs polymorphisms were investigated in various cancer types studies. However, precious studies have reported that the Polymorphisms on TLR1-TLR10 cluster have been associated with increased risk of prostate cancer. However, it has known that TLRs genetic variation is associated with increased the susceptibility to gastric cancer. A same synthetically meta-analysis also confirmed the association of TLRs with increased the gastrointestinal cancer but with decreased prostate cancer risk. Our previous studies have demonstrated a strong link between TLRs polymorphisms and colon cancer and breast cancer in Saudi Arabia population. Similar studies were analyzed with Korean patients with papillary thyroid cancer and their clinic-pathologic features in age matched controls by using direct sequencing. The general objective of this chapter was to investigate the role of different TLRs (i.e., TLR2, TLR4, and TLR6) polymorphisms and their association with cancer development.

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Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile in ovarian cancers

Cited by 9 publications

References 22 publications

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

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

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

Toll-Like Receptors Gene Polymorphism and Susceptibility to Cancer Development

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