Prof. Kari Hemminki took part in The Annual Czech Cancer Research Meeting in Olomouc. Together with prof. Asta Försti, they presented their research in „Genetic predisposition to colorectal cancer: Identification of novel cancer susceptibility genes“.
About 15% of colorectal cancer (CRC) patients have first-degree relatives affected by the same malignancy. However, for most families the cause of familial aggregation of CRC is unknown. To identify novel high-to-moderate-penetrance germline variants underlying CRC susceptibility, we performed whole exome (WES) and whole genome sequencing (WGS) in Polish CRC families showing a Mendelian inheritance pattern. After WES or GWS, we used our in-house developed Familial Cancer Variant Prioritization Pipeline (FCVPP) to identify novel cancer predisposition variants. We identified both nonsense, missense and 5’UTR variants involved in the regulation of innate immune response (SLC15A4), apoptosis and AKT pathway (PTK7), reactive oxygen species and mucus biology (CYBA, TRPM4), Wnt signaling (APCDD1) and histone modification (HDAC5) and in a protooncogene (SRC). Some of the identified variants may show they effect according to a synergistic or polygenic model. Our findings contribute to the identification of unrecognized genetic causes of familial CRC.
