Title

 

Authors

J. Zolezzi

Doctorate School in Pharmacology and Toxicology
Dept. of Pharmacology, Alma Mater Studiorum-University of Bologna 

 

Abstract

The classic epidemiological approach allows the identification of potential risk factors and their possible relation with a particular disease. However, the critical changes that take place after the interaction between organism and risk factor remain unknown. In carcinogenic process early critical changes are of great importance due the fact that they could indicate the establishment and beginning of the process. The objective of molecular epidemiology is the identification of molecular biological markers and the study of their possible significance related with exposure to xenobiotics and with biological events developed at early stages of different diseases. Colorectal Cancer (CRC) has been described as the second most common form of cancer and the second leading cause of cancer death in Europe,and one of the leading causes of cancer-related deaths in USA [1]. Early detection of CRC is one of the proven strategies resulting in a higher cure rate. The current adopted CRC screening procedures include fecal occult blood test and colonoscopy. However, symptoms, like bleeding, appear belatedly in the course of the disease making more difficult the detection and diagnosis of CRC, additionally the prognosis when symptoms appear is generally poor. The early detection and diagnosis of CRC could improve the prognosis of the disease.In order to identify genetic damage biomarkers predictive for CRC risk, it has been evaluated Micronuclei (MN) frequency in peripheral blood lymphocytes from subjects resulted positive to fecal occult blood test (FBT) and examined by colonoscopy, among participants of CRC screening program. Until now study population comprise 75 subjects aged between 50-80 years, resulted positive to FBT and classified by histological lesion at the baseline colonoscopy in three groups: a) Control: normal epithellium (26 subjects, 7 female and 19 males, mean age: 59,3±6,0; b) Adenoma (23 subjects, 10 females and 13 males, mean age: 60,43±6,14); and c) Cancer: carcinoma (26 subjects, 10 females and 16 males, mean age: 67,69±9,76).The MN analysis was performed using the cytokinesis block technique [2]. MN frequency was significantly higher in subjects with histological diagnosis of Cancer than Controls (p = 0,01) and Adenoma (p < 0,05). Also, MN frequency was significantly higher in subjects with Adenoma than Controls (p < 0,05). Multiple regression analysis was applied to investigate the influence of disease status alongside, age, gender and Body Mass Index (BMI). MN frequency was significantly affected by disease status, but not by the other three variables. These results seem to support the concept reported by other autors [3, 4] that an increased MN frequency it is closely related with chromosome damage often see in carcinogenic process. Additionally, this results enhance the value of MN frequency as predictor biomarker of CRC risk providing new perspectives in prevention for Colorectal Cancer.
 
 
[1] World Cancer Research Fund and American Institute for Cancer Research (2007)
 
[2] Fenech M. (2007) Nat Protoc 2(5):1084-104
 
[3] Bonassi S et al. (2007) Carcinogenesis 28:625
 
[4] Karaman A et al. (2008) World J Gastroenterol 14:6835