B16
Differential risk of bowel cancer – Apoptosis and mitosis in the normal mucosa of those with adenomatous and metaplastic Polyps, adenocarcinomas and diverticular disease
Daniel Commane1, Ramesh Arasaradnam1, Charles Rayner1, Mike Bradburn2, John Mathers1
1Newcastle University, Newcastle upon tyne, UK, 2Wansbeck General Hospital, Northumberland, UK
Background
BORICC is an observational study investigating biomarkers of colorectal cancer risk which may be modifiable via dietary intervention. Increased cell turnover in epithelial tissues may be a field change which predisposes to neoplastic development through increasing potential DNA copy errors. We investigated crypt cell kinetics in normal rectal tissue from age and sex matched volunteers shown to have different stages of neoplastic transformation elsewhere in the bowel.
Method.
Biopsies of macroscopically normal mucosa were taken from volunteers with a ‘normal’ bowel exam (n= 48), adenomas (n= 24) metaplastic polyps (n=16) cancers (n= 7) and diverticular disease (DD) (n=10). Individual crypts were separated via microdissection. Each crypt was divided into 10 compartments and mitotic and apoptotic counts were determined for each volunteer.
Results
There were higher levels of apoptosis in individuals with non-inflamed DD (P= 0.07) and metaplastic polyps (P= 0.02) and a non-significant trend towards higher apoptosis in those with adenomatous polyps or cancers than in volunteers with an entirely normal colon.
There was a non-significant trend towards higher mitoses in the normal mucosa of volunteers with colorectal cancer. This trend was most apparent in the normal proliferative zone of the crypt and did not reflect an expansion of this region towards the luminal surface.
Conclusion
Higher apoptosis in those with metaplastic polyps and DD may indicate increased cell damage, higher mucosal tissue turnover and therefore a higher risk of colorectal cancer, this warrants further investigation. We have ongoing efforts to establish relationships between crypt cell kinetics and environmental factors.
