Predicting colorectal cancer risk
Colorectal cancer (CRC) is one of the most common cancers in both men and women. An EU project investigated potential biomarkers for CRC risk prediction.
While several genetic mutations predispose to CRC, these markers are not
predictive enough for clinical application. Alterations in some
important molecular pathways also influence disease risk. By measuring
activity of such pathways, it would be possible to find additional
biomarkers for better prediction of CRC risk.
An EU-funded project CRCINTERMPHEN (Functional characterisation of colorectal cancer predisposition genes and development of intermediate biomarkers of disease risk) tested several factors for CRC prediction. To do so, the project established a bank of over 400 specimens of normal, benign and cancerous colorectal mucosa. In addition to colonic biopsies, the same cohort of patients provided blood samples for DNA and RNA extraction in the study.
Three types of markers were assessed: single-nucleotide polymorphisms (SNPs), telomere lengths (TL) and pathway expression. While SNP alone conferred only slight increase in CRC risk, the length of telomeres (the structural ends of chromosomes) helped to assess cell ageing. Pathway activity provided insight into cellular proliferation and cell death. By assessing the three types of markers, scientists summarised the processes involved in malignant transformation.
CRCINTERMPHEN discovered that both bowel TL and polygenic risk scores may be used as good measures of CRC development. TL markers in blood also correlated with bowel TL measurements. Moreover, assessing blood TL is a less invasive means of risk assessment.
Predictive biomarkers can be used to assign the population to different risk groups. Thus, individuals with the highest polygenic risk score would be seven times more likely to develop CRC than those with the lowest risk score.
The project results provide important knowledge for CRC prognosis and early detection. Strong risk predictors would allow preventive measures to be targeted to those at highest risk of CRC.
published: 2015-10-06