title: 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 polymorphismrs10759931was 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 polymorphismrs2770150was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphismrs4986790was 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.
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Abdelhabib
authors.initials: A
authors.lastname: Semlali
authors.affiliation: Centre de recherche du CHU de Québec, L'Hôtel-Dieu de Québec, Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec, QC, Canada.
authors.forename: Maroua
authors.initials: M
authors.lastname: Jalouli
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Narasimha Reddy
authors.initials: NR
authors.lastname: Parine
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Amri
authors.affiliation: College of Medicine, King Saud University.
authors.forename: Maha
authors.initials: M
authors.lastname: Arafah
authors.affiliation: Department of Women's Imaging, King Fahad Medical City.
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Al Naeem
authors.affiliation: Department of Family Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Abdullah Ajaj
authors.affiliation: Groupe de Recherche en Écologie Buccale, Department of Stomatology, Faculty of Dentistry, Université Laval, Quebec, QC, Canada.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Rouabhia
authors.affiliation: Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Mohammad Saud
authors.initials: MS
authors.lastname: Alanazi
keywords: Saudi population; Toll-like receptor 4; breast cancer; estrogen receptor; innate immunity; single-nucleotide polymorphisms