Primary objective of this study is the identification of familial germline mutations in SPS. Secondary objectives are to get a better insight in the molecular pathway of SPS and associated colorectal carcinoma, to discriminate those family members…
ID
Source
Brief title
Condition
- Gastrointestinal tract disorders congenital
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To identify the SPS causative gene using exome sequencing technique in
well-characterized SPS patients and families.
Secondary outcome
• To give an overview of polyposis and SPS patients identified in a
retrospective PALGA search in a tertiary medical centre over 27 years
• To distinguish different subtypes in phenotypes of patients with serrated and
mixed polyposis
• To confirm the possible genes in additional SPS families, SPS singletons and
exclude it in healthy controls.
• To study the effect of the mutation on protein level
• To elucidate the genetic mechanism underlying the serrated carcinoma pathway
and molecular etiology in SPS
• To identify patients at increased risk for colorectal carcinoma and family
members at increased risk for polyposis or CRC
Background summary
The serrated polyposis syndrome (SPS), formerly known as the hyperplastic
polyposis syndrome, is a relatively rare condition, which has been first
recognized about 10 years ago. Hallmark of SPS is de occurrence of multiple
serrated polyps in the large intestine. SPS is associated with an increased
risk for both patients and their first degree relatives to develop a colorectal
carcinoma. As such, there is evidence for a hereditary behavior of this
syndrome. Unfortunately, to date the initial germline mutation remains unknown.
With this study, we want to identify the genetic mutation associated with SPS.
We want to expand a previous study in only one large SPS family with other
families, singletons and healthy family members to broaden our search for the
genetic background of SPS.
Study objective
Primary objective of this study is the identification of familial germline
mutations in SPS. Secondary objectives are to get a better insight in the
molecular pathway of SPS and associated colorectal carcinoma, to discriminate
those family members at risk for SPS and colorectal cancer from those who are
not at risk, and to diagnose patients in an early phase of the disease.
Study design
This study is a cross-sectional study in all SPS patients diagnosed at our
Gastroenterology, Pathology and Human Genetics departments and their first
degree relatives. All relevant clinical data will be collected in a digital
database. There will be no additional treatment administered, introduced or
recommended to subjects by the study itself. After obtaining written informed
consent, from each individual 10 cc EDTA blood will be sampled for isolation of
DNA. When colonoscopy is performed, healthy colonic tissue samples will be
collected for isolation of DNA. In blood, colon tissue and polyp/tumor tissue
we will search for mutations associated with SPS. To start, DNA will be
analyzed by exome sequencing to identify possible pathogenic mutations. If the
results of the first tests need stronger evidence, in a second run more family
members with SPS will be recruited and included for exome sequencing. If one or
more candidate genes are identified, all family members, both SPS and non-SPS,
and SPS singletons will be analyzed for an association between SPS and the
candidate genes.
Study burden and risks
The physical risks that are introduced to the participants by this study are
considered to be minimal. It is limited to a bruise caused by a single
venapunction for the withdrawal of 10 cc blood. This small amount has no
influence on the health status of the subject. Next to this, there exists a
minimal risk for bleeding associated with taking biopsies during colonoscopy.
The perforation risk after taking biopsies is negligible. The risk for bleeding
(about 2%) or perforation (about 0.01 to 0.1 %) after removing polyps in these
patients is far larger than simple biopsies. The mental burden for the included
subjects in general is predicted to be low.
Geert Grooteplein-Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein-Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
Patients fulfilling the WHO criteria for SPS (5) or first degree family members (both SPS as non-SPS suspects), from identified patients with SPS
Age >= 18 years
Exclusion criteria
Age < 18 years
Incapacitated subjects
Patients with known germline mutations (e.g. mutations in APC or MUTYH)
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 | NL44839.091.13 |