Study title
Predicting tumor development risk by an integrated approach linking diet-related inflammation to colon cancer
Template
Intervention/Observation study
title
Predicting tumor development risk by an integrated approach linking diet-related inflammation to colon cancer
description
The aim of this study was to correlate specific fatty acid profiles of visceral white adipose tissue (WAT)
with inflammatory signatures potentially associated with colorectal cancer. Also this study seeks investigated the role of human visceral fat adipocytes in regulating the functions of innate immunity cells.
startDate
2015-05-14 00:00:00.0
Study type
Human Intervention
Principle Investigator
Roberta Masella / Sandra Gessani, Istituto Superiore di Sanità Viale Regina Elena 299 - 00161 -Rome (Italy) roberta masella@iss.it; sandra.gessani@iss.it
Primary endpoint
The aim of this project is to better understand the mechanistic link connecting dietary components, inflammation and colon cancer. In particular, for the ex-vivo study of this project, we would analyze the effects of n-3 and n-6 fatty acids on the inflammatory status of isolated human adipocytes.
Objectives
1. Identification of individual variations in FA composition underlying the inflammatory signature of white adipose tissue in subjects with or without colorectal cancer 2. Definition of the cross-talk between adipocytes and immune system.
Central conclusion
Adipocyte dysfunctions occur in colorectal cancer patients creating a pro-inflammatory environment that might influence cancer development.The protective potential of docosahexaenoic acid in re-establishing the equilibrium between pro- and anti-inflammatory factors might represent a useful tool for preventive and therapeutic strategies.
Exclusion criteria
"Exclusion’s criteria: clinical evidence of active infection, recent (within 14 days) use of antibiotics or anti-inflammatory drugs, pregnancy,severe mental illness, diabetes, treatment regimens including immunomodulators, hormonal therapies,
family history of cancer. BMI between 25 and 29.9. "
Inclusion criteria
Healthy subjects or Colon Cancer Subjects with BMI between 20 and 25, or higher than 30; Sign written informed consent; Age 28-78
Institute
Istituto Superiore di Sanità (Roma) and Bambino Gesù Children Hospital (Roma)
Country (for multicentre study overall PI)
Italy
Was the study approved by an ethics committee?
Yes
Ethical approval number
CE 13/410 2013
Did the individuals providing data sign informed consent?
Yes
Study design
Case-control
Type of controls
untreated cells
Explanatory text (Give a textual account of the overall design leading to the total number of groups) or provide the study protocol.
"The risk of developing colon cancer (CC) is elevated in the obese population, and the chronic inflammation characterizing obesity provides evidence for a link between inflammation, obesity and cancer. Fatty acids (FAs), key components of white adipose tissue (WAT), are major determinants in inflammation. Our hypothesis is that WAT represents a key regulatory node in inflammation-related colon carcinogenesis.
To understand the mechanistic links connecting dietary components, inflammation and CC, 46 subjects with or without CC have been enrolled and have been asked to respond to a validated face-to-face food frequency questionnaire. We enroll only normal weight or obese subjects, to correlate BMI with dietary components, molecular, and clinical variables.
Nutrition-specific and -omic datasets (whole transcriptome analysis, dietary intake assessment, fatty acid composition, inflammation biomarkers) will be obtained by adipocytes isolated from WAT biopsies of the 46 subjects.
For the ""ex-vivo"" study, to test the hypothesis that distinct FAs can differently modulate signaling pathways affecting specific adipocyte functions, and that these responses may differ on the basis of the category of subject, the effects of pro-inflammatory n-6 arachidonic acid and anti-inflammatory n-3 docosahexaenoic acid (inflammation biomarkers and whole trascriptomic analysis) will be tested on adipocytes isolated from WAT biopsies of 24 out of 46 subjects.
Treatments (Number and types of foods, drugs or other treatments compared)
n-6 arachidonic acid ( AA, 20:4) and n-3 docosahexaenoic acid (DHA, 22:6) have be tested on adipocytes isolated from adipose tissue of participating subjects.
Number of volunteers screened N(M:xx, F: xx)
60 (M:19, F:41)
Number of volunteers enrolled N(M:xx, F: xx)
46 (M:13, F:33)
Number of subjects (Male; Female)
24 (M:9, F:15)
Start of recruitment (Start year or date)
2014-01-01 00:00:00.0
End of recruitment (End year or date)
2016-01-01 00:00:00.0
