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Structural Genomic Variation in TLR4 Gene and Cancer

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Genomics of Pattern Recognition Receptors

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Abstract

Toll-like receptor 4 (TLR4) is one of the key immune system effectors playing the main role in recognition of viruses and bacteria. Dysregulation of the TLR4 signaling owing to single nucleotide polymorphisms may alter the ligand binding and balance between pro- and anti-inflammatory cytokines, therefore modulating the risk of chronic inflammation and cancer. According to the data represented in this chapter, TLR4 gene polymorphisms may be associated with at least twelve types of cancer. The most intensively investigating TLR4 gene polymorphisms are Asp299Gly (rs4986790) and Thr399Ile (rs4986791). It seems to be that Asp299Gly and Thr399Ile are related to increased risk of precancerous gastric lesions, and, possibly, gastric cancer and lymphoma. Thr399Ile also may be connected with gallbladder cancer and nasopharyngeal carcinoma, and both these polymorphisms apparently have no impact on risk of prostate cancer. Several other TLR4 gene polymorphisms are also probably associated with various malignant tumors. However, the data about many TLR4 gene polymorphisms and their associations with different types of cancer are conflicting, and further large, well-designed, comprehensive studies in various populations are necessary for solution of this problem.

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  1. Epidemiology, Kemerovo State Medical Academy, Voroshilova Str. 22A, Kemerovo, Russia, 650029

    Anton G. Kutikhin

  2. Siberian Branch, Res Inst Cardiovascular Diseases, Russian Academy of Medical Sciences, Sosnovy Blvd. 6, Kemerovo, Russia, 650002

    Arseniy E. Yuzhalin

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Kutikhin, A.G., Yuzhalin, A.E. (2013). Structural Genomic Variation in TLR4 Gene and Cancer. In: Genomics of Pattern Recognition Receptors. Springer, Basel. https://doi.org/10.1007/978-3-0348-0688-6_3

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