The association between Huntington's disease and cancer before and after the Huntington's diagnosis - a two-phase study

Date of ISAC Approval: 
Lay Summary: 
Huntington's disease (HD) is a genetic disorder associated with abnormal movements, psychiatric disturbances and progressive cognitive decline. It usually presents in mid-life (mean age of onset in the UK is 52 years). Death usually occurs between 10 and 20 years after the onset of symptoms. The underlying biochemical basis of HD suggests that the genetic abnormality may provide protection against cancer. Indeed, several previous studies have suggested that patients with HD are substantially less likely to be diagnosed with malignant disease than those without HD. The difficulty in interpreting these studies is that the HD populations all had symptomatic (diagnosed) disease. It is possible that symptomatic patients with HD either fail to present with symptoms suggestive of malignancy; or, if they do, their healthcare professionals fail to investigate them because of their poor health and/or prognosis. In the proposed study we plan to investigate the frequency of diagnoses of cancer in patients who have already been diagnosed with symptomatic HD as well as in those who have yet to have their HD diagnosed both compared to appropriately matched controls
Technical Summary: 
HD is an autosomal dominant condition usually presenting in mid-life. It is due to an expanded CAG repeat on the short arm of chromosome 4. As a consequence the gene product, an abnormal form of the protein huntingtin, has an expanded polyglutamine tract that accumulates in neuronal cells and causes cell death. It has been postulated that the mutant HD gene product protects against malignant disease and previous studies (Sorensen and Fenger 1992, 1999; Ji et al 2012) have claimed to show this. These studies, however, were conducted in people with symptomatic HD and it is possible that such patients either failed to present with relevant symptoms; or that their healthcare professionals failed to investigate them because of their poor state of health and/or their poor prognosis. We plan to undertake a two phase study of the frequency of cancer diagnoses among both symptomatic, and presymptomatic, patients with HD compared with the frequency of cancer diagnoses in matched controls. By examining the frequency of cancer in symptomatic HD patients it should be possible to confirm or refute the previous evidence suggesting a reduced frequency of malignant disease in patients with diagnosed HD. By examining the frequency of malignancy in presymptomatic HD patients, compared to controls, we hope to avoid the potential diagnostic bias that may have affected previous studies among those with manifest HD.
Health Outcomes to be Measured: 
An incident cancer diagnosis Resource costs; consultation and drug costs

Sir Michael Rawlins - Chief Investigator - National Institute for Health and Clinical Excellence - NICE
Mr Daniel Dedman - Researcher - CPRD
Ian Douglas - Researcher - London School of Hygiene & Tropical Medicine (LSHTM)
Ian Pavord - Researcher - University of Oxford
Dr Krishnan Bhaskaran - Researcher - London School of Hygiene & Tropical Medicine (LSHTM)
Professor Liam Smeeth - Researcher - London School of Hygiene & Tropical Medicine (LSHTM)
Nancy Wexler - Researcher - Columbia University
Professor Stephen Evans - Researcher - London School of Hygiene & Tropical Medicine (LSHTM)