الفهرس 
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Abstract
Colorectal cancer (CRC) is the fourth most common cancer and account for 8.5 % of all incident cases worldwide.CRC is one of the most common types of cancer in humans. The incidence of colorectal cancer in Egypt is 3.9 – 6 % of the malignant neoplasms of the digestive system. The colon cancer ranks the sixth of the male and the fifth of the female cancer sites with a mean age of 65 years. Rectal carcinomas are detected in younger age than colonic carcinomas. It is reported that both sexes are equally affected.
The insulin-like growth factor (IGF) system has been shown to play a critical role in growth, development and maintenance of normal homeostasis. It is composed of receptors, ligands (IGF-I and IGF-II) and a family of binding proteins (IGFBPs). IGF-I is a single polypeptide chain that shares 62% homology with proinsulin. Liver is the major site of production of IGF-I, which is regulated by growth hormone (GH) levels. IGF-I exerts its biologic effects through activation of insulin-like growth factor type 1 receptor (IGF-IR). Binding of ligands causes activation of downstream cascades resulting in proliferative, differentiative and anti-apoptotic effects.
Colorectal carcinogenesis results from an accumulation of specific molecular alterations, and increased cellular turnover may enhance the rate at which these alterations accumulate. Evidence strongly conclude that GH and IGF-I are acritical determinants of colon cancer. IGF receptors are found in human colon cancers, and full length messenger RNAs for IGFs have been detected in human tumor cells. Exogenous IGF-I stimulates proliferation of human colorectal cancer cells, whereas blockage of the IGF-I receptor inhibits tumor cell growth. Individuals with acromegaly, a disease of somatic growth caused by increased growth hormone and IGF-I, have an increased incidence of colonic cancer.
Circulating GH is in large part bound to GH binding protein (GHBP) and acts via the ubiquitously expressed GH receptor (GHR). Many of the actions of GH are mediated by insulin-like growth factor-I (IGF-I), which can act in an endocrine, autocrine and paracrine manner
Elevated insulin level may also increase hepatic GH receptor number and activity, reflected by an increase in the level of circulating growth hormone binding protein (GHBP). This effect may lead to a rise in GH regulated hepatic IGF-I and IGFBP-3 production, with a greater increase in level of circulating IGF-I relative to IGFBP-3.
Therefore the current work aims to study the relation between the levels of insulin like growth factor-I (IGF-I) and GH and correlate them with tumor grade and tumor stage.
This study was conducted on 31 patients with colorectal cancer and 17 healthy controls. Serum blood samples were taken after fasting 12h. The serum was separated by centrifugation at 3000(g and preserved at -80°C till use.
All cases were subjected to full clinical examination and the following laboratory investigations:
1- Determination of GH by Enzyme Amplified Sensitivity Immunoassay (EIAgen) technique.
2- Determination of serum Insulin-like growth factor-I level using enzyme-labeled chemiluminescent immunometric assay (ELCIA).
The following results were obtained from the current study:
1- Serum GH level is significantly higher in colorectal cancer patients than control group (P = 0.001).
2- No significant difference was observed between GH serum levels in different tumor grades (P=0,352)
3- No significant difference was observed between GH serum levels in different tumor stages (P = 0.678).
4- Serum IGF-I level is significantly higher in patients with CRC than controls
(P= 0.001).
5- No significant difference was observed between IGF-I serum levels in different tumor stages or tumor grades (P = 0.429, 0.322; respectively).
6- There was a positive significant statistical correlation between GH and IGF-I
(r = +0.358 & p = 0.048).
7- IGF level have a diagnostic value in colorectal cancer diagnosis (area under the curve 79.6 %, sensitivity 87.1% and specificity 52.9 p = 0.001).
8- GH showed a higher diagnostic performance than IGF-I (area under the curve 84.1 % sensitivity 100 % and specificity 58.8 % p = 0.000).
from the above results it was concluded that there is a positive correlation between the increased levels of IGF-1 and GH and colorectal cancer and this is consistent with the hypothesis that the levels of IGF-1 and GH may play a role in the development of colorectal cancer and so they could be used as a diagnostic biomarkers for colorectal cancer. Also this study showed that tumor stages (B and C) or grades (II and III) don’t affect IGF-I and GH serum levels.