In our World Cancer Research Fund project we will evaluate different forms of vitamin D in the development of colorectal neoplasms in people with Lynch syndrome.
More insight into the role of lifestyle factors, such as vitamin D, in the development of colorectal neoplasms may lead to intervention studies and, ultimately, prevention programmes or specific recommendations for these people with an inherited high risk of cancer. – Dr Franzel van Duijnhoven
The role of vitamin D in the development of colorectal neoplasms in persons with Lynch syndrome
People with Lynch syndrome (LS) are born with a difference in one of their genes, which is called a mutation. Because of this mutation, they have a high risk of developing tumours in the large bowel during their life.
Being overweight and smoking have consistently been shown to strongly increase the risk of these large bowel tumours in people with LS.
Vitamin D may play a role in these observations. High levels of vitamin D in the body have been associated with a decreased risk of large bowel tumours. Since vitamin D concentrations have never been investigated in LS before, we aim to unravel the role of vitamin D in the development of large bowel tumours in people with LS.
Aims and objectives
Our main prediction is that higher vitamin D concentrations are associated with a decreased large bowel tumour risk in people with LS. Vitamin D levels will be measured in the blood, through genetic data and through intake via diet and supplements. Furthermore, we will evaluate whether vitamin D plays a role in the association between being overweight and smoking in relation to large bowel tumour risk in people with LS.
How it will be done
For the proposed international project, we will use already available data and blood samples from 2,785 people with LS, who participate in the GEOLynch cohort study, the Colon Cancer Family Registry Cohort and the Ohio Colorectal Cancer Prevention Initiative. Blood samples and genetic data will be analysed for vitamin D concentrations in all participants.
Clinical data during the first years of follow-up have already been gathered. Remaining follow-up data on tumour diagnoses will be collected via pathology, medical and cancer registry reports throughout the proposed project. Subsequently, all demographic, dietary, lifestyle, genetic, laboratory and clinical data will be pooled into one central database.
We will analyse this database to determine whether the different forms of vitamin D are related to the risk of large bowel tumours. In addition, we will investigate the role of vitamin D in the association between being overweight as well as smoking in relation to large bowel tumour risk.
Although large bowel cancers in people with LS are only about 3% of the total cases of large bowel cancer, this still comes down to more than 55,000 new large bowel cancer cases each year worldwide. Furthermore, one in 279 people in western countries are estimated to have LS. This emphasises the need to unravel how lifestyle can influence the risk of large bowel tumours for people with LS.
More insight into the role of lifestyle factors, such as vitamin D, in the development of large bowel tumours may lead to intervention studies and, ultimately, prevention programmes or specific recommendations for these people with an inherited high risk of large bowel cancer.