Significantly lower incidence of cancer among patients with Huntington disease - An apoptotic effect of an expanded polyglutamine tract?

BACKGROUND. The authors of this study have previously observed that cancer is rarely reported on the death certificates of patients with Huntington di sease. This study was undertaken to investigate whether this disorder is as sociated with a lower incidence of cancer. METHODS, A total of 694 patients with Huntington disease who had survived a t least to age 45 pears during the period 1943-1993, and 695 individuals at risk and at least age 55 years during the same period, were selected from the Danish Huntington Disease Registry. The occurrence of cancer was determ ined from the files of the Danish Cancer Registry and compared with nationa l incidence rates for various categories of tumors. RESULTS. The overall incidence of cancer was significantly lower among pati ents with Huntington disease, but not among their healthy relatives. The st andardized incidence ratio for the Huntington patients was 0.6 with a 95% c onfidence interval of 0.5-0.8. The lower incidence was seen for cancers of all major tissues and organs except the buccal cavity and the pharynx, CONCLUSIONS, The lower incidence of cancer among patients with Huntington d isease seems to be related to intrinsic biologic factors. One explanation m ap be that the modified protein, huntingtin, encountered in Huntington dise ase protects against cancer by inducing or increasing the rate of naturally occurring programmed cell death in preneoplastic cells. Cancer 1999;86:134 2-6. (C) 1999 American Cancer Society.