Some missense substitutions in RNASEL have been reported to interact with other genetic and environmental factors to increase early-onset risk of disease, e.g. RNASEL:c.1385G > A (p.Arg462Gln) and early-onset hereditary non-polyposis colorectal cancer in MSH2 or MLH1 pathogenic mutation carriers [18, 19]. This evidence concerns the gene RNASEL and hereditary nonpolyposis colon cancer.