Polymorphisms of Toll-like receptor 4 (TLR4) as a key player in cell proliferation, apoptosis, and angiogenesis have been linked to colorectal cancer (CRC) in different populations. We aimed in this study to determine genetic associations of TLR4 variants with CRC progression in Egyptian patients. Genotype and allelic frequencies of Asp299Gly (rs4986790) and Thr399Ile (rs4986791) were compared between 127 CRC patients and 141 healthy Egyptians using restriction fragment length polymorphism, and were correlated to clinicopathological findings. Results revealed that the variant alleles (G of Asp299Gly) and (T of Thr399Ile) were significantly associated with CRC among Egyptians. Confirmed by haplotype analysis, AT and GT haplotypes were more frequent in CRC patients than controls with increased CRC odds (OR = 3.54 and 3.45, 95% CI = 1.48–8.48 and 1.09−10.83, respectively). In addition, the G allele of Asp299Gly SNP was observed to be significantly associated with progressive CRC, including stage IV (P = .001), grade III (P = .025), N2 lymph nodes (P = .020), and metastasis (P = .001). On the other hand, Thr399Ile variant did not show any association with tumor behavior. Taken together, we conclude a significant association of Asp299Gly and Thr399Ile variants with the risk of development of CRC in Egypt. Asp299Gly variant, but not the Thr399Ile variant, may serve as a biomarker of this disease progression in Egyptian population.

Toll样受体4（TLR4）的多态性作为细胞增殖，凋亡和血管生成的关键因素，已与不同人群的结直肠癌（CRC）相关联。我们在这项研究中的目的是确定TLR4变异与埃及患者CRC进展的遗传关联。使用限制性片段长度多态性比较了127例CRC患者和141例健康的埃及人的Asp299Gly（rs4986790）和Thr399Ile（rs4986791）的基因型和等位基因频率，并与临床病理结果相关。结果显示，埃及人中的变异等位基因（Asp299Gly的G）和（Thr399Ile的T）与CRC显着相关。通过单倍型分析证实，CRC患者的AT和GT单倍型比CRC优势增加的对照组更为频繁（OR = 3.54和3.45，95％CI = 1.48–8.48和1.09-10.83）。此外，P = .001），III级（P = .025），N2淋巴结（P = .020）和转移（P = .001）。另一方面，Thr399Ile变体没有显示出与肿瘤行为的任何关联。两者合计，我们得出结论，Asp299Gly和Thr399Ile变体与埃及发生CRC的风险显着相关。Asp299Gly变异体，而非Thr399Ile变异体，可以作为埃及人群中这种疾病进展的生物标记。