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

Abstract

Abdelhabib Semlali,1 Maroua Jalouli,2 Narasimha Reddy Parine,1 Abdullah Al Amri,1 Maha Arafah,3 Abdulrahman Al Naeem,4 Sanaa Abdullah Ajaj,5 Mahmoud Rouabhia,6 Mohammad Saud Alanazi1 1Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Centre de recherche du CHU de Québec, L’Hôtel-Dieu de Québec, Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec, QC, Canada; 3College of Medicine, King Saud University, 4Department of Women’s Imaging, King Fahad Medical City, 5Department of Family Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Groupe de Recherche en Écologie Buccale, Department of Stomatology, Faculty of Dentistry, Université Laval, Quebec, QC, Canada 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. Keywords: Toll-like receptor 4, single-nucleotide polymorphisms, breast cancer, Saudi population, innate immunity, estrogen receptor

Keywords

• Toll-like receptor 4 Single-nucleotide polymorphisms (SNPs) Breast cancer Saudi population