Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

A wide variety of genes have been associated with colorectal cancer (CRC) development and progression. Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domain (NOD)-containing proteins (Nods) are two important families of microbial sensors. They play a critical role in the host initial sensing of microbial agents by recognition of conserved structures. SIRT1 is one of the mammalian homologues of silent information regulator 2 (Sir2). SIRT1 expression increased in various human malignant tumors such as colon and breast cancer. This study aimed to assess whether polymorphism in TLR4; (rs4986790), (rs4986791), NOD2/CARD15; (rs2066847) and SIRT1 (rs7895833), all involved in innate immune response and inflammation, as well as serum TLR4 levels is associated with the risk for CRC in an Egyptian population of 103 CRC patients and 30 healthy controls. Results showed that polymorphisms in the TLR4; Asp299Gly (rs4986790), Thr399Ile (rs4986791), NOD2/CARD15; 1007fs (3020insC) (rs2066847) were not associated with CRC at p=0.46, p=0.31 and p=1, respectively. Higher serum level of TLR4 was observed in CRC patients than in the controls at p<0.0001. SIRT1 (rs7895833) GG genotype was associated with CRC at p< 0.0001. Higher SIRT1 G allele frequency was found in the rectal cancer patients than in the colon cancer patients at p=0.035. Our data suggest that SIRT1 (rs7895833) but not TLR4; Asp299Gly (rs4986790), Thr399Ile (rs4986791) and NOD2/CARD15; 1007fs (3020insC) (rs2066847) SNPs has significant association with CRC. Furthermore, CRC may be associated with higher level of serum TLR4

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