| Titel | Clinical and lifestyle factors as determinants of colorectal tumours in high-risk populations |
|---|---|
| Looptijd | 06 / 2005 - 12 / 2010 |
| Status | Afgesloten |
| Dissertatie | Ja |
| Onderzoeknummer | OND1309936 |
| Dikke darmkanker is een van de meest voorkomende vormen van kanker in Nederland. Dikke darmpoliepen worden gezien als een voorstadium van dikke darmkanker. Wanneer deze poliepen voortijdig worden weggehaald kan het ontstaan van kanker worden voorkomen. Bij mensen met dikke darmpoliepen wordt iedere 6 jaar een darmonderzoek gedaan en eventuele poliepen weggehaald. Het aantal poliepen die gevonden worden, de grootte van de poliep en het soort poliepen kunnen de kans op het terugkeren van poliepen bepalen. Het is niet duidelijk of voedingsgewoonten en andere leefgewoonten, zoals roken en een hoge alcoholconsumptie het terugkeren van darmpoliepen kunnen beinvloeden. Sommige mensen hebben een aangeboren gevoeligheid voor stoffen in onze voeding en sigarettenrook. Deze mensen zouden in combinatie met bepaalde leefgewoonten extra gevoelig kunnen zijn. Dikke darmkanker komt in sommige families meer voor dan in de rest van Nederland: het zogenaamde Hereditary Non-Polyposis Syndroom (HNPCC) is een erfelijke vorm van darmkanker. Het risico op het krijgen van darmkanker in deze families is erg groot, maar toch krijgt niet iedereen met deze ziekte te maken. Het is nog onbekend of voeding en leefgewoonten in combinatie met gevoeligheid voor voedingsstoffen en sigarettenrook ook binnen deze families het risico op darmkanker kunnen beinvloeden. In het voorgestelde onderzoek maken we gebruik van twee reeds bestaande studiepopulaties, nl. 768 mensen met dikke darm poliepen en 248 mensen uit families met het HNPCC syndroom. In deze studie willen we deze mensen volgen in de tijd om te kunnen bestuderen of poliepkenmerken (waaronder beschadigingen van het groeiregulerende APC gen), voeding en leefgewoonten het risico op darmpoliepen en darmkanker in deze hoog-risico groepen zouden kunnen beinvloeden. |
| The identification and removal of adenomatous polyps and post- polypectomy surveillance are important for the control of colorectal cancer. Thirty percent of patients with resected sporadic adenomas develop new adenomas within three years. Morphological characteristics, size and number of previous adenomas are known to increase adenoma recurrence two- to threefold. However, it is not clear whether other tumour characteristics (e.g. somatic mutations, DNA methylation of growth regulating genes), dietary habits and lifestyle factors, in combination with genetic susceptibility, may influence risk of recurrence. Also, it is not known which dietary advice to give to those at risk for Hereditary Non-Polyposis Colorectal Cancer (HNPCC), i.e. carriers of an inherited mutation in mismatch repair genes. Since colorectal tumours do not occur in all mutation carriers, it is expected that dietary habits and lifestyle influence colorectal tumour risk in these individuals. Our previous case-control studies on the occurrence of sporadic and HNPCC colorectal tumours (KWF projects LUW 96-1374 and LUW 98-1687) showed an increased tumour risk among smokers and those with a high intake of alcohol, and, among HNPCC families only, a low intake of dietary fibre. In addition, we observed that associations with smoking and alcohol were modified by inherited differences in metabolic enzymes, and that the mutation patterns in tumours, were associated with lifestyle habits. Aim. To evaluate whether characteristics of previous adenomas, diet and lifestyle factors, in combination with genetic susceptibility are determinants of colorectal tumour risk among high-risk subjects, i.e. sporadic adenoma patients (risk of recurrence) and HNPCC- families (first occurrence and recurrence). Plan of investigation. A prospective study will be conducted to evaluate tumour risk after 3 to 10 years of follow-up among sporadic adenoma patients (n=768) and members of HNPCC-families (n=500) who participated in our previous case-control studies and expressed their interest in subsequent studies. In these previous studies, tumour characteristics of adenomas (location, morphology, size, number, somatic mutations, DNA methylation), diet, lifestyle, and genetic susceptibility have been assessed at index endoscopy between 1997 and 2003. Among sporadic patients, post-polypectomy surveillance is conducted every six years, according to protocol. This implies that after 4 years of follow-up in the proposed study 1 or 2 colonoscopies will be conducted, in which 200-300 recurrent tumours may be found. Among high-risk members of HNPCC families, screening is conducted every 1 to 2 years, according to protocol, which implies that about 3 to 5 colonoscopies will be conducted during the follow-up period. Currently, 145 family members are included with a previous colorectal tumour and 103 members who never had a colorectal tumour. Additional mutation carriers will be recruited and included in this prospective investigation. Clinical characteristics of new colorectal tumours will be assessed, and among all participants, dietary and lifestyle information will be updated and blood samples (sporadic group) or buccal swaps (HNPCC family members) will be collected to evaluate biomarkers of intake and genetic polymorphisms respectively (e.g. genetic variants related to folate and fatty acid metabolism and ornithine decarboxylase). Possible results/Relevance for cancer research. This prospective investigation provides the possibility to assess the influence of previous tumours (histology, number, architecture, somatic mutations, DNA methylation), dietary and other lifestyle habits, and genetic susceptibility on colorectal tumour risk among high risk individuals. Results will not only add to our knowledge of colorectal carcinogenesis, but may also provide practical tools for dietary and lifestyle advice to those with previous polyps or with an inherited high risk of colorectal cancer. |
| Penvoerder | Afdeling Humane Voeding (WUR) |
|---|---|
| Financier | KWF Kankerbestrijding |
| Promotor | Prof.dr.ir. E. Kampman |
|---|---|
| Promotor | Prof.dr.ir. P. van 't Veer |
| Co-promotor | Dr. F.M. Nagengast |
| Co-promotor | Prof.dr. H.F.A. Vasen |
| Promovendus | Ir. A. Botma |
| Themagebied | VLAG3-D2 Individual |
|---|
| A70000 | Volksgezondheid en gezondheidszorg |
|---|---|
| A71000 | Voeding |
| D23120 | Kanker |
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