MSH2 and malignant colon neoplasm: We have to remember that in most hereditary cancers, the number of high penetrance causative genes is usually only two or three—e.g., BRCA1 and BRCA2 in breast cancer, or APC, MLH1 and MSH2 in colon cancer—but many studies have tried unsuccessfully to discover a causative gene with a high penetrance for FNMTC.