الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Colorectal cancer (CRC) is one of the major health problems worldwide. It is a multifactorial disease involving both genetic and environmental factors. CRC has vague or nonspecific symptoms, so it is generally diagnosed in the advanced stage. Furthermore, the mortality of colorectal cancer is strongly related to the disease stage. Currently, the major available strategies for screening and diagnosis of colorectal cancer include colonoscopy and stool-based testing. Histopathology examination via colonoscopy is considered as the golden standard.
In addition, tumor markers like CEA and CA 19-9 are clinically used as routine tumor markers to monitor disease progression of colorectal cancer and response to treatment. Nevertheless, these markers have limited use in early diagnosis and cancer screening due to their low sensitivity and specificity.
Since the conventional methods for CRC screening and diagnosis are either ineffective or invasive thus there is an urgent need to develop an accurate CRC screening strategy based on noninvasive biomarkers, which could be well accepted and widely used in asymptomatic population for early prediction.
A SNP is the most common type of human genetic variation and extensive researches have been conducted about the association between certain SNPs and CRC.
IL-17A is one of six family members of IL-17. It is a cytokine produced mainly by activated T cells, while its receptor is distributed ubiquitously, it acts on a wide range of cell types and participates in the regulation of diverse immune functions, such as the expression of various inflammatory cytokines and chemokines, production of antibodies, and activation and recruitment of leukocytes, with a crucial role in the development of multiple autoimmune diseases as rheumatoid arthritis, psoriasis, multiple sclerosis and Inflammatory Bowel Disease ,also it has a role in development of cancers as gastric cancer, and lung cancer and CRC by nurturing angiogenesis via promoting VEGF production from cancer cells and production of tumor invasion factors as MMP-9, MMP-13, CCR6 and PGE2 which is involved in the migration of CRC cells, also it stimulates the recruitment of neutrophils which can create an immunosuppressive environment and impair anti-tumor immune responses. As a final effect, a possible induction of the cancer development may occur.
Changes in the expression of IL-17A has been reported to be associated with the risk of multiple cancers including CRC. One of the most common polymorphisms of IL-17A rs2275913 (A/G) located at the promoter region of IL-17A gene and contains a single Guanine to Adenine base transition at position 197 from the start codon of the IL-17A gene, it is linked to transcribing higher levels of mRNA due to the higher affinity of the A-allele for NFAT (nuclear factor of activated T-cells) transcription factor which is an important regulator of IL17A gene expression leading to more efficient IL-17A secretion. As a final effect, a possible induction of the cancer development may occur.
In this regard, our study aimed to investigate the clinical utility of the IL-17A gene polymorphism (A/G) (rs2275913) in CRC patients in order to explore it’s association with CRC disease.
The study was conducted on 35 CRC patients (group I), 20 patients with IBD serving as a pathological control (group Π) and 20 healthy control subjects (group III). The study population was recruited from Ain Shams University Hospitals. All individuals enrolled in this study were subjected to full history, general clinical examination and laboratory investigations as CBC, CRP, ESR, CEA and CA 19.9. Radiological examination for CRC patients by CT for localization of tumor, tumor size, differentiation, lymph node metastasis and histopathological characteristics were obtained from the patients medical record.
To achieve our goal, genotyping for the polymorphism of the IL-17A rs2275913 (G/A) was performed on all participants of the study by real time PCR.
Our study showed no statistically significant difference regarding the genotype frequencies of the 17A rs2275913 (A/G) polymorphism between CRC patients group, IBD patients group and normal control group
We tried to investigate the relation of genotypic distribution of 17A rs2275913 (A/G) polymorphism between early stages (I and II) and late stages (III and IV) of CRC but our results showed no statistical significant difference.
Our study showed a high statistically significant difference in the level of CRP, ESR, CEA and CA19.9 being higher in CRC group compared with healthy control group while Hb level is lower in CRC patients, also a high statistically significant difference in ESR and CRP between IBD and normal control group being higher in IBD patients while hemoglobin level is lower. Additionally, a highly statistical significant difference in the level of CEA and CA19.9 being higher in CRC group compared with IBD group.
The discrepancy between results obtained from our study and other studies could be explained by the difference in ethnic and racial groups studied, differences in sample sizes and selection criteria of the patients, the differences in methodology and lack of standardization in these methodologies.
In conclusion, our study had demonstrated the presence of IL-17A rs2275913 (AA) genotype in both CRC and IBD patients however, it did not confirm the presence of significant association between IL-17A rs2275913 (A/G) polymorphism and CRC in Egyptian population.