Is Telomere Length shortening a Predictive Biomarker for Cancer Risk in Ulcerative Colitis?

Aims: Neoplastic progression in Ulcerative Colitis (UC) is accompanied by genetic abnormalities and telomere shortening is a candidate for producing such genomic instability. Our overall goal is to examine if telomere shortening can distinguish UC patients at greatest risk of dysplasia/Colorectal Cancer (CRC). We hypothesize that continuous telomere length shortening may correlate with UC progression.

Methods: Telomere length measurements were assessed using Quantitative Fluorescence In Situ Hybridisation (Q-FISH) and confocal microscopy in longitudinal biopsies from 16 UC patients without dysplasia/CRC and 14 UC patients who progressed to dysplasia and 5 to CRC. Approximately 8 images were analysed for each case.

Results: There was no statistical difference in average telomere lengths comparing flat versus polyploid dysplasia cases. Telomere lengths in dysplasia and cancer lesions did not show significant evidence of telomere shortening. 2 of 14 dysplasia patients did however show telomere shortening in previous surveillance biopsies prior to diagnosis of dysplasia. 3 of 16 UC patients without dysplasia or CRC displayed a statistically significant decline in telomere lengths in longitudinal follow up biopsies.

Conclusions: Telomere length measurements may be used as a useful screening tool in identifying those patients at high risk of CRC development and may require more extensive surveillance.