Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

Abstract

Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-βcan be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC.