The purpose of this study is to investigate the role of adipokines-secretion in visceral adipose tissue and its influence on the risk for esophageal adenocarcinoma. Examination of adipose tissue may provide important insight into mechanistic links…
ID
Source
Brief title
Condition
- Metabolism disorders NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Collected samples will be immediately frozen in liquid nitrogen and stored at
-80°C until total RNA preparation.
Total RNA will be extracted from adipose tissue and expression levels of the
genes of interest are quantified with real-time-quantitative-PCR (RTq-PCR). We
will use at least 2 housekeeping genes as an endogenous reference to compensate
for variations in input RNA amounts.
Secondary outcome
Dependent on the results of our study on gene expression we will possibly
measure the size of adipocytes in those 2 groups later in this study.
Previously validated methods include: direct microscopy and manual/automated
measurement of diameters from digital images.
Influence of other patient characteristics on adipokines production/development
of cancer:
Patient information on prior weight loss, tumor stage and chronic diseases will
be collected from the hospital information system and preoperative status.
Other study parameters:
Patient information on smoking, alcohol use, use of PPI and LES-relaxing and
other drugs, history of reflux, DM, preoperative plasma-glucose-values as well
as levels of HbA1c, cholesterol, triglycerides, CRP etc. will be collected from
the patients* charts/ Elpado hospital information system if available.
Background summary
In the last 3 decades the incidence of esophageal adenocarcinoma has been
increasing rapidly in the United States and western Europe. Recent reviews
showed that being overweight or obese (BMI of > 25 kg/m2 or > 30kg/m2 resp.)
is associated with an approximately 2-fold increase of risk for esophageal
adenocarcinoma compared to individuals with normal weight.
It is known that high BMI and abdominal fat are related to gastro-esophageal
reflux disease (GERD) and Barrett*s disease. Especially visceral adipose tissue
seems to play an important role as a risk factor in this context. It has been
found to be larger in individuals that develop Barrett's disease than in a
control population.
The exact mechanism of the effect of visceral obesity on the development of
Barrett's and as a consequence adenocarcinoma still remains unclear. Increased
intragastric pressure and GE-pressure gradient probably play a role in this
context but don*t explain all the risk.
Another possible explanation could lie in adipose tissue itself. Adipose tissue
functions as both an energy store and an active endocrine organ. It secretes a
range of hormones, growth factors, enzymes, cytokines, matrix proteins and
complement factors (collectively termed adipokines), among them leptin,
adiponectin, Interleukin-1, -6, -8, -10 and TNF-α. Visceral fat is known to be
more metabolically active than subcutaneous fat and alterations in serum level
of adipokines have been linked with several cancers. Adipokines also seem to
have a local effect on Barrett*s carcinogenesis.
Study objective
The purpose of this study is to investigate the role of adipokines-secretion in
visceral adipose tissue and its influence on the risk for esophageal
adenocarcinoma. Examination of adipose tissue may provide important insight
into mechanistic links for the observed association between higher body fat and
risk of esophageal cancer. Esophageal adenocarcinoma still has a 5-year
survival rate of only about 15% because patients usually present late when
already in advanced stages. It is therefore important to identify the risk
factors for this cancer and detect subjects with a higher risk earlier.
Primary Objective:
Is there a difference in gene expression of adipokines in omental fat tissue in
subjects with esophageal adenocarcinoma compared to subjects without Barrett*s
disease or cancer, independent of BMI?
Possible secondary Objectives:
Does the size of omental adipocytes differ between the 2 groups? Does the size
have an influence on gene expression of adipokines and is there a difference
between the two groups?
Which patient characteristics (i.e. smoking, prior weight loss, tumor stage
etc) have an effect on the relation between adipokines production in fat tissue
and the development of esophageal adenocarcinoma?
Study design
This will be a pilot study with the design of a case-control study.
Cases and controls will be matched for sex and BMI.
Study burden and risks
The additional risk arising from this study is negligible for the patient.
By removing a small amount of fat tissue during surgery minor bleeding can
occur but those bleedings can be treated easily and directly.
The operation will not be prolonged through this procedure and neither will the
hospital stay of the patients. No control visits will be necessary besides the
ones related to the patients' disease.
's-Gravendijkwal 230
3015 CE Rotterdam
NL
's-Gravendijkwal 230
3015 CE Rotterdam
NL
Listed location countries
Age
Inclusion criteria
Patients with newly diagnosed esophageal adenocarcinoma who are referred to surgery at the Erasmus Medical Center will be included in our study. Sex- and BMI-matched patients who are referred for surgery at the Erasmus Medical Center for other reasons than esophageal cancer/ Barrett*s disease/GERD will be included as controls.
Exclusion criteria
- Patients with severe weight loss (>10% during the last 3 months before surgery)
- Patients without information on height and weight at the time of surgery
- Patients with a BMI < 20
- Patients with severe co-morbidities or diseases with a possible effect on body weight and/or fat distribution
- Patients in the control group with a history of Barrett*s esophagus/GERD
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL32476.078.10 |