Toll-like receptor-4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women

Abstract

The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody. Our results demonstrated an increase in TLR-4 expression in estrogen receptor (ER)−, postmenopausal breast cancer patients compared to normal. We also demonstrated that the G allele of single-nucleotide polymorphism rs10759931 was found to be significantly higher in frequency among patients (36.3%) compared to the control group (26.7%), suggesting that this polymorphism is strongly associated with the development of breast cancer in this ethnic population. In addition, the TLR-4 polymorphism rs2770150 was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphism rs4986790 was also found to be associated with this malignancy in the ER− patient groups. Our results suggested firstly that the variation in TLR-4 gene expression may influence breast cancer development and secondly a closely linked association between TLR-4 gene polymorphism and ER status. Our study provides support for a better understanding of the implication of TLR-4 polymorphism in breast tumorigenesis and for its eventual use as a cancer biomarker.

Toll-like receptor 6 expression, sequence variants, and their association with colorectal cancer risk

“…In humans, the immune system consists of two classes: innate immunity and adaptive immunity 6. An association between the dysregulation of innate immunity and cancer development risk has been reported previously in our own and other studies 7-9. Of the two immune system classes in humans 10,11, the innate system is responsible for nonspecific immune responses mediated by phagocytotic cells, such as dendritic cells, macrophages, and neutrophils, and represents a first line defensive mechanism for protecting the host from invading microbial pathogens, pollutants, and endogenous dangerous molecules 12,13.…”

Toll‐like receptor 4 polymorphisms in Saudi population with cardiovascular diseases

“…Recently, our studies and others have identified three SNPs in TLR4 , including rs2770150, rs10759931, and rs4986790 that were associated with colon and breast cancer in the Saudi population (Semlali, Jalouli, et al, ; Semlali et al, ). These SNPs were selected based on the HapMap database (http://www.hapmap.org) due to their functional properties.…”

Comprehensive assessment of association between TLR4 gene polymorphisms and cancer risk: a systematic meta-analysis

“…Polymorphisms of rs4986790 and rs4986791 in exon 3, leading respectively to the substitution of Asp299Gly and Thr399Ile amino acid and downregulating the expression of several genes in the TLR4 TRAM/TRIF signaling pathway [ 34 ], was associated with endotoxin hyporesponsiveness [ 35 ], gram-negative septic shock [ 36 ] and atherogenesis [ 37 ]. However, analyses focusing on them did not reach a consensus on cancer risk and some proved they had a nonnegligible impact on breast cancer [ 11 , 13 ] and digestive cancer [ 23 , 26 ], while the others believed that no evident could support significant association with gastric cancer [ 38 , 39 ], bladder cancer [ 40 ], prostate cancer [ 20 ], leukemia [ 41 ]. To minimized the effects of sample size, a large amount of publications on variant cancers were collected in this study and the consequence reflected there was a significant association between rs4986791 polymorphism and the decrease of cancer risk while polymorphism of rs4986790 was found irrelevant to cancer risk.…”