Potential Role of Toll-like Receptor 2 Expression and Polymorphisms in Colon Cancer Susceptibility in the Saudi Arabian Population

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2018 Dec 12

PMID 30532554

Citations 19

Authors

Abdelhabib Semlali

Narasimha Reddy Parine

Nouf S Al-Numair

Mikhlid Almutairi

Yousef M Hawsawi

Abdullah Al Amri

Abdulrahman M Aljebreen

Maha Arafah

Majid A Almadi

Nahla Ali Azzam

Othman Alharbi

Mohammad Saud Alanazi

Affiliations

Soon will be listed here.

Abstract

Background: Inflammation is a fundamental factor that contributes to the development and progression of several types of cancer including colon cancer. Toll-like receptors () 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 and their association with colon cancer.

Methods: Real-time PCR and immunohistochemistry were used to investigate gene expression and to evaluate the potential risk of predisposition to colon cancer caused by three tagging single-nucleotide polymorphisms (SNPs) on , 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, was highly expressed in epithelial colon cancer cells and both mRNA and protein levels, and significantly decreased in tumor tissues compared to normal tissues. Two of three SNPs increased the risk of colon cancer. However, 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 rs3804100 showed a significant association with patients less than 57 years. In silico analysis of the 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, 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 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.

Citing Articles

Variants rs3804099 and rs3804100 in the Gene Induce Different Profiles of TLR-2 Expression and Cytokines in Response to Spike of SARS-CoV-2.

Flores-Gonzalez J, Monroy-Rodriguez Z, Falfan-Valencia R, Buendia-Roldan I, Fricke-Galindo I, Hernandez-Zenteno R Int J Mol Sci. 2024; 25(20).

PMID: 39456843 PMC: 11507191. DOI: 10.3390/ijms252011063.

The known and unknown about attention deficit hyperactivity disorder (ADHD) genetics: a special emphasis on Arab population.

Mahrous N, Albaqami A, Saleem R, Khoja B, Khan M, Hawsawi Y Front Genet. 2024; 15:1405453.

PMID: 39165752 PMC: 11333229. DOI: 10.3389/fgene.2024.1405453.

Study of gene polymorphisms in Toll-like receptor 2 in patients with acute lymphoblastic leukemia.

M Alkhulaifi F, Alonaizan R, Rady A, Alomar S Heliyon. 2024; 10(13):e33754.

PMID: 39040297 PMC: 11261853. DOI: 10.1016/j.heliyon.2024.e33754.

Analysis of Epidemiological Factors and SNP rs3804100 of for COVID-19 in a Cohort of Professionals Who Worked in the First Pandemic Wave in Belém-PA, Brazil.

Silva M, Silva C, Marinho R, Cabral J, Gurrao E, Dos Santos P Genes (Basel). 2023; 14(10).

PMID: 37895256 PMC: 10606513. DOI: 10.3390/genes14101907.

Role of toll-like receptor in the pathogenesis of oral cancer.

Bhardwaj A, Prasad D, Mukherjee S Cell Biochem Biophys. 2023; 82(1):91-105.

PMID: 37853249 DOI: 10.1007/s12013-023-01191-8.

References

Caws M, Thwaites G, Dunstan S, Hawn T, Lan N, Thuong N . The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog. 2008; 4(3):e1000034. PMC: 2268004. DOI: 10.1371/journal.ppat.1000034. View

Pohl C, Hombach A, Kruis W . Chronic inflammatory bowel disease and cancer. Hepatogastroenterology. 2000; 47(31):57-70. View

Gordon S . Pattern recognition receptors: doubling up for the innate immune response. Cell. 2003; 111(7):927-30. DOI: 10.1016/s0092-8674(02)01201-1. View

Marino M . Xenoestrogens challenge 17β-estradiol protective effects in colon cancer. World J Gastrointest Oncol. 2014; 6(3):67-73. PMC: 3955780. DOI: 10.4251/wjgo.v6.i3.67. View

Georgel P, Macquin C, Bahram S . The heterogeneous allelic repertoire of human toll-like receptor (TLR) genes. PLoS One. 2009; 4(11):e7803. PMC: 2773936. DOI: 10.1371/journal.pone.0007803. View

Zarember K, Godowski P . Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol. 2002; 168(2):554-61. DOI: 10.4049/jimmunol.168.2.554. View

Alanazi M, Pathan A, Abduljaleel Z, Arifeen Z, P Shaik J, Alabdulkarim H . Association between PARP-1 V762A polymorphism and breast cancer susceptibility in Saudi population. PLoS One. 2014; 8(12):e85541. PMC: 3877358. DOI: 10.1371/journal.pone.0085541. View

Zeng H, Pan K, Zhang Y, Zhang L, Ma J, Zhou T . [The correlation between polymorphisms of Toll-like receptor 2 and Toll-like receptor 9 and susceptibility to gastric cancer]. Zhonghua Yu Fang Yi Xue Za Zhi. 2011; 45(7):588-92. View

de Oliveira J, Silva A . Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population. World J Gastroenterol. 2012; 18(11):1235-42. PMC: 3309913. DOI: 10.3748/wjg.v18.i11.1235. View

10.

Sauna Z, Kimchi-Sarfaty C . Understanding the contribution of synonymous mutations to human disease. Nat Rev Genet. 2011; 12(10):683-91. DOI: 10.1038/nrg3051. View

11.

Kim M, Park S, Kim S, Park H, Eun Y, Kwon K . Association of Toll-like receptor 2 polymorphisms with papillary thyroid cancer and clinicopathologic features in a Korean population. J Korean Med Sci. 2012; 27(11):1333-8. PMC: 3492667. DOI: 10.3346/jkms.2012.27.11.1333. View

12.

Chen C, Zibiao H, Ming Z, Shiyi C, Ruixia L, Jie W . Expression pattern of Toll-like receptors (TLRs) in different organs and effects of lipopolysaccharide on the expression of TLR 2 and 4 in reproductive organs of female rabbit. Dev Comp Immunol. 2014; 46(2):341-8. DOI: 10.1016/j.dci.2014.05.008. View

13.

Hendrickse C, Jones C, Donovan I, Neoptolemos J, Baker P . Oestrogen and progesterone receptors in colorectal cancer and human colonic cancer cell lines. Br J Surg. 1993; 80(5):636-40. DOI: 10.1002/bjs.1800800531. View

14.

Karin M, Lawrence T, Nizet V . Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. Cell. 2006; 124(4):823-35. DOI: 10.1016/j.cell.2006.02.016. View

15.

Yu H, Kortylewski M, Pardoll D . Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2006; 7(1):41-51. DOI: 10.1038/nri1995. View

16.

Sheng W, Yong Z, Yun Z, Hong H, Hai L . Toll-like receptor 4 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review. Arch Med Sci. 2015; 11(4):699-707. PMC: 4548027. DOI: 10.5114/aoms.2015.53288. View

17.

Priyadarshini A, Chakraborti A, Mandal A, Singh S . Asp299Gly and Thr399Ile polymorphism of TLR-4 gene in patients with prostate cancer from North India. Indian J Urol. 2013; 29(1):37-41. PMC: 3649598. DOI: 10.4103/0970-1591.109982. View

18.

Takeda K, Akira S . Toll-like receptors in innate immunity. Int Immunol. 2004; 17(1):1-14. DOI: 10.1093/intimm/dxh186. View

19.

Milne A, Carneiro F, OMorain C, Offerhaus G . Nature meets nurture: molecular genetics of gastric cancer. Hum Genet. 2009; 126(5):615-28. PMC: 2771140. DOI: 10.1007/s00439-009-0722-x. View

20.

Tchorzewski M, Lewkowicz P, Dziki A, Tchorzewski H . Expression of toll-like receptors on human rectal adenocarcinoma cells. Arch Immunol Ther Exp (Warsz). 2014; 62(3):247-51. PMC: 4024133. DOI: 10.1007/s00005-013-0260-z. View