INTRON SPLICE ACCEPTOR SITE SEQUENCE VARIATION IN THE HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER GENE HMSH2

Common but weakly penetrant mutations of certain genes may confer an i ncreased susceptibility to colorectal cancer and account for a proport ion of 'sporadic' cases. We analysed DNA from 111 colorectal cancer ca ses and 114 controls for a specific candidate sequence variation in th e hereditary non-polyposis colorectal cancer gene hMSH2. The variant s equence was found in a quarter of individuals, and there was no differ ence between cancer cases and controls, according to age of developmen t of cancer or presence of family history. It thus appears that this p articular sequence variation is a polymorphism rather than a mutation which increases cancer susceptibility.