Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

OncoTargets and Therapy, Dec 2016

Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients Abdelhabib Semlali,1 Narasimha Reddy Parine,1 Abdullah Al Amri,1 Arezki Azzi,2 Maha Arafah,3 Muhammad Kohailan,1 Jilani P Shaik,1 Majid Abdulrahman Almadi,4,5 Abdulrahman M Aljebreen,3,4 Othman Alharbi,3,4 Nahla Ali Azzam,3,4 Mahmoud Rouabhia,6 Mohammad Saud Alanazi1 1Genome Research, Department of Biochemistry, College of Sciences, King Saud University, 2College of Medicine, Al Imam Muhammad Ibn Saud Islamic University, 3College of Medicine, King Saud University, 4Division of Gastroenterology, King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia; 5Division of Gastroenterology, McGill University Health Center, Montreal General Hospital, Montreal, 6Groupe de Recherche en Écologie Buccale, Département de Stomatologie, Faculté de Médecine Dentaire, Université Laval, Québec City, QC, Canada Objective: The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. Methods: In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene’s promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. Results: The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. Conclusion: The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer. Keywords: Innate, immunity, TLR polymorphisms, rs187084, rs352139, rs352144

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://www.dovepress.com/getfile.php?fileID=34109

Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

OncoTargets and Therapy association between TLR-9 polymorphisms and colon cancer susceptibility in saudi arabian female patients PowerdbyTCPDF(ww.tcpdf.org) Objective: The authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population. Methods: In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene's promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues. Results: The authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area. Conclusion: The findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females The innate immune system is the first line of defense against pathogens and tissue injury.1 The human immune system is a well-coordinated network of cells, organs, and glands that protects the body from foreign invaders. Therefore, an optimized immune system is the key to health and longevity, and the immune system plays a crucial role in preventing cancer. Toll-like receptors (TLRs) appear to be involved in the first line of defense against invading pathogens, initiating inflammatory responses and playing a key role in immune cell regulation, survival, and proliferation. Through their role in the immune system, TLRs are potential tools for curing and preventing cancer. It is estimated that between 10 and 13 TLR families (named TLR-1 to TLR-13)2-5 are activated by various ligands expressed in different types of immune cells. These receptors are located on the cell surface, and TLR-3, TLR-7, TLR-8, and TLR-9 are localized to the endosomal/lysosomal compartment in most mammalian species. Human TLR-9, Innate; immunity; TLR polymorphisms; rs187084; rs352139; rs352144 - open access to scientific and medical research O r i g i n a l r e s e a r c h abdelhabib semlali 1 n arasimha reddy Parine 1 abdullah al amri 1 arezki azzi 2 Maha arafah 3 Muhammad Kohailan1 Jilani P shaik 1 Majid abdulrahman almadi 4,5 abdulrahman M aljebreen 3,4 Othman alharbi 3,4 n ahla ali azzam 3,4 Mahmoud rouabhia 6 Mohammad saud alanazi 1 1g enome r esearch, Department of Biochemistry, college of sciences, King saud University, 2c ollege of Medicine, a l imam Muhammad ibn saud islamic University, 3c ollege of Medicine, King saud University, 4Division of g astroenterology, King Khalid University h ospital, King s aud University, r iyadh, Kingdom of saudi arabia; 5Division of g astroenterology, Mcg ill University h ealth c enter, Montreal g eneral hospital, Montreal, 6g roupe de recherche en Écologie Buccale, Département de stomatologie, Faculté de Médecine Dentaire, Université laval, Québec city, Qc , canada Introduction which has been mapped to chromosome 3p21.3,2 spans ~5 kb and contains two exons. The TLR-9 gene encodes a protein of 1032 amino acids2 and is preferentially expressed by B cells and plasmacytoid dendritic cells.6 TLR-9 is one of the most important receptors for the initiation of innate immune responses against intracellular pathogens. Unlike other products of the TLR gene family, which are membrane-bound 8 pattern recognition receptors, TLR-9 is localized on the endo-210 plasmic reticulum membrane (in the resting state) or on the l-Ju endosomal/lysosomal membrane (after ligand stimulation and 2n1 trafficking);7,8 however, TLR-9 interacts with unmethylated 72o CpG DNA from bacteria and some viruses.9,10 Alternatively, .613 TLR-9 functions through the MyD88-dependent pathway, .17 leading to nuclear factor-kappa-B (NF-κB) activation, .354 cytokine secretion, and inflammatory response.11,12 To date, /yb TLR-9 is the only TLR for which a systemically administered .com specific agonist has shown substantial evidence of anticancer ss activity in human clinical tria (...truncated)


This is a preview of a remote PDF: https://www.dovepress.com/getfile.php?fileID=34109

Abdelhabib Semlali, Narasimha Reddy Parine, Abdullah Al Amri, Arezki Azzi, Maha Arafah, Muhammad Kohailan, Jilani P Shaik, Majid Abdulrahman Almadi, Abdulrahman M Aljebreen, Othman Alharbi, Nahla Ali Azzam, Mahmoud Rouabhia, Mohammad Saud Alanazi. Association between TLR-9 polymorphisms and colon cancer susceptibility in Saudi Arabian female patients, OncoTargets and Therapy, 2016, pp. 1-11, DOI: 10.2147/OTT.S106024