Relationship between Arg753Gln Toll-like receptor 2 and Asp299Gly Toll-like receptor 4 genetic variations and susceptibility to colorectal cancer in southern Iran

Paper description: Comprehensive genetic studies in different populations contribute to a better understanding of the genetic mechanisms of diseases. Examination of genetic variations of regulators of immune and inflammatory responses, Arg753Gln TLR2 (rs5743708) and Asp299Gly TLR4 (rs4986790), evaluated for the first time in colorectal cancer patients and healthy controls in southern Iran, showed that Arg753Gln TLR2 but not Asp299Gly TLR4 can be considered as a risk factor for colorectal cancer incidence, especially in men. This result contributes towards a detailed assessment of the role of TLR genetic variations in colorectal cancer. Abstract: Variations in Toll-like receptor 2 ( TLR2 ) and Toll-like receptor 4 ( TLR 4) encoding genes have been associated with tumorigenesis through the disruption of immune and inflammatory responses. The aims of this study were to evaluate the two single nucleotide polymorphisms (SNPs) of the genes Arg753Gln TLR2 (rs5743708) and Asp299Gly TLR4 (rs4986790) in colorectal cancer patients in southern Iran. Colorectal cancer patients and healthy controls were included in this study (150 Persian subjects in each group). Blood samples were used for genotyping by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between these SNPs and colorectal cancer and clinicopathological factors, including age, gender, tumor stage and differentiation were also investigated. A significant association was found between Arg753Gln TLR2 SNP and colorectal cancer. This SNP was significantly more frequent in male patients. However, there was no association between Asp299Gly TLR4 and colorectal cancer. Therefore, Arg753Gln TLR2 SNP can be considered as a risk factor for colorectal cancer incidence in southern Iran, especially in men. Further investigations in other populations are recommended in order to assess the association of this SNP with colorectal cancer. https://doi.org/10.2298/ABS180812043H Received: August 12, 2018; Revised: September 18, 2018; Accepted: September 18, 2018; Published online: September 26, 2018 How to cite this article: Hosseini SV, Mojtahedi Z, Beizavi Z, Khazraei H, Zamani M. Relationship between Arg753Gln Toll-like receptor 2 and Asp299Gly Toll-like receptor 4 genetic variations and susceptibility to colorectal cancer in Southern Iran. Arch Biol Sci. 2018;70(4):775-9.

[1]  A. Bolourian,et al.  Streptomyces, shared microbiome member of soil and gut, as 'old friends' against colon cancer. , 2018, FEMS microbiology ecology.

[2]  A. Sameer,et al.  Role of TLR4 gene polymorphisms in the colorectal cancer risk modulation in ethnic Kashmiri population – A case–control study , 2017 .

[3]  P. Mokarram,et al.  The Correlation Between Single Nucleotide Polymorphism Patterns and Colorectal Cancer in the Iranian Population , 2016 .

[4]  S. Anant,et al.  Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-κB Mediated Inflammation in Colon Cancer Patients , 2016, PloS one.

[5]  B. Geramizadeh.  Molecular Biomarkers of Colorectal Cancer: A Review of Published Articles From Iran , 2015 .

[6]  J. Cleveland,et al.  Gender disparity in the role of TLR2 in post-ischemic myocardial inflammation and injury. , 2015, International journal of clinical and experimental medicine.

[7]  U. Vogel,et al.  Polymorphisms in NFKB1 and TLR4 and Interaction with Dietary and Life Style Factors in Relation to Colorectal Cancer in a Danish Prospective Case-Cohort Study , 2015, PloS one.

[8]  M. Mohammadianpanah.  Characteristics of the Patients With Colorectal Cancer: Epidemiologic Study or Pathology Report-Based Study , 2014, Iranian Red Crescent medical journal.

[9]  E. Brusina,et al.  Correlation between genetic polymorphisms within IL-1B and TLR4 genes and cancer risk in a Russian population: a case-control study , 2014, Tumor Biology.

[10]  Jing-Yuan Fang,et al.  Positive association between Toll-like receptor 4 gene +896A/G polymorphism and susceptibility to gastric carcinogenesis: a meta-analysis , 2013, Tumor Biology.

[11]  S. Huber,et al.  Sex differences in TLR2 and TLR4 expression and their effect on coxsackievirus-induced autoimmune myocarditis. , 2013, Experimental and molecular pathology.

[12]  A. Leite-Moreira,et al.  Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans. , 2013, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[13]  Y. Bignon,et al.  Positive link between variant Toll-like receptor 4 (Asp299Gly and Thr399Ile) and colorectal cancer patients with advanced stage and lymph node metastasis , 2013, Tumor Biology.

[14]  P. Mokarram,et al.  Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer , 2012, Molecular Biology Reports.

[15]  Yuan Yuan,et al.  Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis. , 2012, Gene.

[16]  A. E. Silva,et al.  Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population. , 2012, World journal of gastroenterology.

[17]  R. Mandal,et al.  Association of Toll-like receptor (TLR) 2, 3 and 9 genes polymorphism with prostate cancer risk in North Indian population , 2012, Molecular Biology Reports.

[18]  H. Shin,et al.  Sequence variants of toll-like receptor 4 (TLR4) and the risk of prostate cancer in Korean men , 2012, World Journal of Urology.

[19]  P. Mokarram,et al.  Epigenetic and genetic analysis of WNT signaling pathway in sporadic colorectal cancer patients from Iran , 2011, Molecular Biology Reports.

[20]  T. Murano,et al.  Tissue expression of Toll-like receptors 2 and 4 in sporadic human colorectal cancer , 2011, Cancer Immunology, Immunotherapy.

[21]  H. Seow,et al.  Variant Toll-like receptor4 (Asp299Gly and Thr399Ile alleles) and Toll-like receptor2 (Arg753Gln and Arg677Trp alleles) in colorectal cancer. , 2011, Iranian journal of allergy, asthma, and immunology.

[22]  M. Abreu,et al.  Pathogen recognition receptors, cancer and inflammation in the gut. , 2009, Current opinion in pharmacology.

[23]  R. Malekzadeh,et al.  Epidemiology and molecular genetics of colorectal cancer in iran: a review. , 2009, Archives of Iranian medicine.

[24]  M. Abreu,et al.  Role of Toll-like receptors in gastrointestinal malignancies , 2008, Oncogene.

[25]  E. El-Omar,et al.  A functional polymorphism of toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors. , 2007, Gastroenterology.

[26]  E. Guinó,et al.  Polymorphisms within inflammatory genes and colorectal cancer , 2006, Journal of Negative Results in BioMedicine.

[27]  J. Terzic,et al.  Microsatelite GT polymorphism in the toll‐like receptor 2 is associated with colorectal cancer , 2006, Clinical genetics.

[28]  B. Xia,et al.  Polymorphism of CD14 gene but not the mutation of TLR4 gene is associated with colorectal cancer in Chinese patients , 2006, Journal of gastroenterology and hepatology.

[29]  M. Kinoshita,et al.  Sex differences in cytokine production and surface antigen expression of peripheral blood mononuclear cells after surgery. , 2005, American journal of surgery.