Broadening risk profile in familial colorectal cancer type X; increased risk for five cancer types in the national Danish cohort

BACKGROUND: Familial colorectal cancer type X (FCCTX) is a phenotypically defined subset of hereditary colorectal cancer with unknown and potentially heterogeneous genetic aetiology. FCCTX has been characterized as a colorectal cancer-specific syndrome, which we herein challenge by estimating the risk for extra-colorectal cancer in the Danish FCCTX cohort. METHODS: Through the national hereditary non-polyposis colorectal cancer (HNPCC) register, 213 families fulfilling the Amsterdam I criteria and showing retained mismatch repair (MMR) function were identified. In here, sex and age-specific incidence rate ratios (IRR) were calculated for 30 extra-colorectal cancer types in comparison with the general Danish population. RESULTS: In total, 494 extra-colorectal cancers developed with significantly increased risks for cancers of the urinary tract, breast, stomach, pancreas, and eye tumours. The age groups at increased risks were 30–49 years for gastric cancer, 30–69 years for female breast cancer, 50–69 years for ocular melanoma and above age 70 for pancreatic cancer and urothelial cancer. CONCLUSIONS: Danish FCCTX families show an increased risk of several extra-colorectal cancer types. This observation may indicate unidentified disease-predisposing genetic variants in this phenotypically defined subset of hereditary colorectal cancer and calls for awareness during genetic counselling and follow-up.