Identification of novel colorectal cancer predisposition genes

There is clear evidence that clinical genetic counseling for hereditary cancer saves lives and relieves anxiety. Our aim is to identify novel genes that predispose to familial colorectal cancer. We follow the empirical gene discovery paradigm by identifying high-risk families diagnosed with the same cancer in several family members. Such families and samples are identified from the world’s largest biobank of 16,000 familial cancers in Szczecin. For this study we identified 15 colorectal cancer families with several affected family members. Germline DNA from cases and unaffected family members are sequenced genome-wide at the DKFZ core facility, one of Europe’s top sequencing centers. Based on the proof-of-principle study on melanoma, a single family may allow identification of a high-risk variant when the new genome-wide sequencing technology is applied. In that example, the detected variant targeted a transcription factor binding site which turned out to be the most common gene variant in melanoma yet described, with implications to prognosis. The present project aims at cancer prevention in identifying novel high-risk variants for which predictive gene testing can be established.EGA study EGAS00001005118