Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population
Received 17 March 2018
Accepted for publication 2 July 2018
Published 14 November 2018 Volume 2018:11 Pages 8127—8141
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Jianmin Xu
Abdelhabib Semlali,1,2 Narasimha Reddy Parine,2 Nouf S Al-Numair,3,4 Mikhlid Almutairi,5 Yousef M Hawsawi,3 Abdullah Al Amri,2 Abdulrahman M Aljebreen,6,7 Maha Arafah,6 Majid A Almadi,6,7 Nahla Ali Azzam,6,7 Othman Alharbi,6,7 Mohammad Saud Alanazi2
1Groupe de Recherche en Écologie Buccale, Département de stomatologie, Faculté de Médecine Dentaire, Université Laval, Quebec City, QC, Canada; 2Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia; 4College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia; 5Zoology Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia; 6College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 7Division of Gastroenterology, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia
Background: Inflammation is a fundamental factor that contributes to the development and progression of several types of cancer including colon cancer. Toll-like receptors (TLRs) and their signaling pathways have been reported to be associated with chronic inflammation and thereby induced cancer. Our aim was to investigate the expression and polymorphisms of TLR2 and their association with colon cancer.
Methods: Real-time PCR and immunohistochemistry were used to investigate TLR2 gene expression and to evaluate the potential risk of predisposition to colon cancer caused by three tagging single-nucleotide polymorphisms (SNPs) on TLR2, including rs3804100, rs4696480, and rs3804099. TaqMan assay was conducted on samples from 115 patients with colon cancer and 102 age- and sex-matched normal individuals.
Results: We found that, TLR2 was highly expressed in epithelial colon cancer cells and both TLR2 mRNA and protein levels, and significantly decreased in tumor tissues compared to normal tissues. Two of three TLR2 SNPs increased the risk of colon cancer. However, TLR2 rs3804099 increased the risk of colon cancer development by more than 3.8- and 5-fold in female patients and patients aged less than 57 years, respectively. The T allele of TLR2 rs3804100 showed a significant association with patients less than 57 years. In silico analysis of the TLR2 nucleotide substitution in SNP rs3804100 and rs3804099 determined that 67% and 70% probability of these single nucleotide variants alter splicing phenotypes, rs3804100 more specifically result on activating an additional splice site. Genotype and allele frequencies of rs4696480 were similar between the overall study populations. Thus, TLR2 rs4696480 appear to be not involved in colon cancer in our study population.
Conclusions: There was a significant link between innate immunity deregulation through disruption of the TLRs and potential development of colon cancer. These SNPs can be used as screening markers for predicting colon cancer risk earlier in life to implement necessary prevention.
Keywords: colon cancer, gene expression, genotyping, polymorphism, Toll-like receptors, innate immunity
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