Positive link between variant Toll-like receptor 4 (Asp299Gly and Thr399Ile) and colorectal cancer patients with advanced stage and lymph node metastasis

• Published in: Tumor biology Vol. 35; no. 1; pp. 545 - 551
• Main Authors: Omrane, Ines, Baroudi, Olfa, Kourda, Nadia, Bignon, Yves-Jean, Uhrhammer, Nancy, Desrichard, Alexis, Medimegh, Imen, Ayari, Hager, Stambouli, Nejla, Mezlini, Amel, Bouzayenne, Hssan, Marrakchi, Raja, Benammar-Elgaaid, Amel, Bougatef, Karim
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 2014; Springer Nature B.V
• Subjects: Adult; Aged; Alleles; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Female; Genetic Association Studies; Genotype; Humans; Lymph Nodes - pathology; Lymphatic Metastasis; Lymphocyte receptors; Lymphoma; Male; Metastasis; Middle Aged; Neoplasm Staging; Polymorphism; Polymorphism, Single Nucleotide; Research Article; Toll-Like Receptor 4 - genetics; Tunisia; Tunisia; Lymph node metastasis; Clinicopathological characteristics; Polymorphisms; Tunisian population; TLR4; Colorectal cancer
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-013-1075-6

Toll-like receptors (TLRs) are considered as major endotoxin-signaling receptor and as crucial sensors of innate immunity. TLRs recognize pathogen-associated molecular patterns; induce effectors genes involving inflammatory cytokines and therefore initiation of adaptative immune responses against pathogens. Recently, it has been shown that TLRs are involved in tumor progression. In fact, increased level of TLR4 is associated with progression of colon malignancies. Even, TLR4 polymorphism has been shown associated with susceptibility to have colorectal cancer. Our study aimed to investigate an association between TLR4 Asp299Gly (D299G) and Thr399Ile (T399I) polymorphisms in Tunisian patients with colorectal cancer. Using a primer extension method (SNaPshot), we genotyped two variants of TLR4 D299G and T399I in 100 patients with colorectal cancer and 140 healthy controls in Tunisian population. Interesting, we noted a significant association between T399I polymorphism and tumor differentiation (
p
 = 0.027) and tumor architecture (
p
 = 0.02) in colorectal cancer (CRC) patients. We also showed a significant association of D299G with an increased risk of advanced stage (
p
 = 0.03). Finally, we observed a positive link between D299G and T399I polymorphisms and CRC patients with lymph node (
p
 = 0.00024;
p
 = 0.0005, respectively) and metastasis (
p
 = 0.001;
p
 = 0.002, respectively). However, we found no evidence to support a significant association between TLR4 D299G and T399I polymorphisms and colorectal cancer susceptibility. Our findings suggest that TLR4 D299G and T399I polymorphisms are significantly associated with clinical features variables. TLR4 polymorphisms may serve as biomarker of disease progression. Therefore, our results need confirmation in even larger studies.