What happens to adiponectin, resistin and apelin-12 in colorectal adenomas? A cross sectional study.

Colorectal adenomas are precancerous neoplastic lesions which may potentially differentiate to the colorectal carcinoma. We investigated whether adiponectin, resistin and apelin 12 serum levels might change in case of colorectal neoplasia. Aims In this study we intended to determine relationship between serum levels of adiponectin, resistin, apelin-12 and presence of colorectal adenoma using case-control approach.


Introduction
Colorectal adenomas are commonly encountered precancerous lesions which may potentially differentiate to colon carcinoma. There is a lot of risk factor in the development of colorectal adenomas. These are content of food (e.g. high-fat, low fiber, salt, smoked meat), smoking, low physical activity and family history [1][2][3][4].
There is increasing evidence that obesity is related with the development of colorectal neoplasia [5]. Increased incidence of colorectal adenoma was observed in patients with metabolic syndrome [6]. Although this, there are conflicting results related with visceral fat and colorectal adenoma risk some of which reveal increased risk, but some not [7,8].
Chronic state of low grade inflammation is another causal relation between obesity and colorectal neoplasia [9].
Although colorectal carcinogenesis was related with visceral fat accumulation and insulin resistance; such relation has not yet been settled for adenoma development [10].
Increased level of insulin has an IGF-1 like effect on colorectal cells which induce colorectal neoplastic development [11]. It is now better understand that adipose tissue is not only an energy reservoir, but also an endocrine organ which secretes adipocyte derived cytokines such as adiponectin and resistin [12,13]. Understanding of etiology of colorectal adenomas and identifications of risk factors for development of colorectal adenomas is an important issue for prevention of colorectal cancer.
Once adipose tissue was known to be storage organ, nowadays it is noticed to be an active organ producing various different proteins. Adiponectin an adipocyte derived adipocytokine was shown to be decreased in patients with insulin resistance, obesity and colorectal adenoma [14,7,15]. It probably interferes with carcinogenesis [16]. Another adipocyte derived hormone namely resistin was also shown to increase in central obesity and insulin resistance [17]. Apelin-12 is recently discovered adipocytokine, serum level of which positively correlates with insulin resistance [18].
In this study we intended to determine relationship between serum levels of adiponectin, resistin, apelin-12 and presence of colorectal adenoma using case-control approach.

Materials And Methods
Patients: Patients undergoing screening colonoscopy in the Abant Izzet Baysal University Hospital Gastroenterology Polyclinics between years 2010 and 2013 were selected for study. Antropometric measurements were performed by trained medical stuff. Patients who were smoking, known diabetes mellitus, chronic renal disease, chronic hepatic disease, malignancy, hypertension, colitis, colorectal surgery and previously performed colonoscopic examination were excluded from this study. Subjects were grouped according to whether adenoma is present or not. Study has been performed in accordance with ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. The study protocol was approved by Düzce University Ethic Comity. Written informed consent was taken from all participants.
Biochemical analysis: All blood samples were obtained after fasting in the morning and centrifuged for 10 min at 1200 g. Serum specimens were stored at -70 ᵒ C until laboratory analysis. Equal procedures were used in collection, handling, transport and storage of all samples to standardize preanalytical factors which could affect laboratory assessment.
Minimum detectable dose of insulin is 0.25 µIU/mL. Intra-assay and inter-assay precision were CV (%): <5 % and <10 %, respectively. Pathologic examination: All specimens were analysed in patalogy department. All paraffin blocks were stained with heamotoxilen and eosin staining and evaluated under light microscope. Adenomatous polyps were grouped as; tubuler, tubulovillous and villous.
Adenomatous polyps were grouped as severe, moderate and mild dysplasic; so as to assess the risk of colon cancer development. Gender distribution was not different between groups (p = 0.318). There was no difference between groups in the proportions of age, BMI, WC and mean arterial blood pressure (all p > 0.05) ( Table-1). The histology of adenomas was 23 (88.5%) tubular adenoma, 2 (7.7%) mix serrated and tubular adenoma and 1 (3.8%) serrated adenoma respectively. According to the neoplastic differentiation; 6 (23.1%) mild dysplastic adenomas, 11 (76.9%) severe dysplastic adenomas were detected. The family frequency of colorectal cancer was significantly higher in patients with adenomas (p = 0.024). Fat consumption and Occupation were not statistically significant between groups (p > 0.05 for each). HOMA-IR, adiponectin, resistin and apelin-12 serum levels were not statistically different between adenomatous and non-adenomatous groups (p = 0.603, p = 0.642, p = 0.890, p = 0.618; respectively) ( Table-2). We also compared serum levels of adiponectin, resistin and apelin-12 into three groups including histological differentiation of adenomas as non-adenoma, adenoma with mild dysplasia, adenoma with severe dysplasia. Only, the median value of the Severe dysplasia significantly higher than the other two groups. (p = 0.014) ( Table-3 Other important subject is insulin resistance. HOMA-R measurement was not statistically different between groups. Although colorectal cancer development is more commonly associated with insulin resistance, there are conflicting data related with insulin resistance and adenoma development in patients with colorectal adenomas [23][24][25][26].
Colorectal adenomas were not related with insulin resistance in metabolically healthy obese people [27]. Further studies are necessary to identify the impact of insulin resistance on the development of colorectal adenoma.
Adiponectin insulin sensitizing adipocyte derived protein secreted from adipose tissue [28]. Adiponectin has an anti-angiogenic and anti-tumor properties. In our study serum adiponectin levels correlated with adenoma number. In terms of serum adiponectin level; there were no differences in between groups. There were conflicting data related with There are some limitations in this study. These are low number of study sample, cross sectional design and absence of tissue sample histochemical analysis.
As a conclusion we can suggest that adiponectin and resistin did not increased in colorectal adenomas. Although this; apelin-12 does increase in severe dysplastic adenomas and might be a candidate marker for detecting dysplastic colorectal adenomas.      Figure 1 Serum level of apelin-12 levels were presented in groups according to neoplastic differantiation.