Huntington's Linked to Reduced Cancer Risk

Megan Brooks

April 13, 2012

April 13, 2012 — Patients with Huntington's disease (HD) or other polyglutamine (polyQ) diseases appear to have a reduced risk for development of cancer, results of a Swedish population-based study suggest.

Researchers found a significantly and consistently reduced incidence of cancer overall and of cancers of specific sites and types in patients with HD, spinobulbar muscular atrophy (SBMA), or hereditary ataxia (HA), relative to the general population of Sweden.

"Our findings suggest a common mechanism in patients with polyQ diseases that protects against the development of cancer, and expansion of the polyQ tracts is likely," report Jianguang Ji, MD, from the Centre for Primary Health Research, Lund University and Skåne University Hospital, Malmö, Sweden, and colleagues.

Their study was published online April 12 in Lancet Oncology.

Using the Swedish Hospital Discharge Register and Outpatient Registry, the researchers identified 1510 patients with HD, 471 with SBMA, and 3425 with HA and linked data on these patients to the Swedish Cancer Registry.

After accounting for confounding factors such as age, sex, period, geographic region, and socioeconomic status, the incidence of cancer was found to be significantly lower among patients with polyQ diseases than in the general population.

Table. Cancer Cases and Standardized Incidence Ratios (SIRs) with PolyQ Disease

PolyQ Disease Cancer Cases SIR (95% Confidence Interval)
HD n (%) 91 (6.0) 0.47 (0.38 - 0.58)
SBMA n (%) 34 (7.2) 0.65 (0.45 - 0.91)
HA n (%) 421 (12.3) 0.77 (0.70 - 0.85)

Dr. Ji and colleagues note that the decrease in cancer risk was even more pronounced before the diagnosis of polyQ diseases, suggesting that "some of the causal factors predisposing to these disorders might be protective against the development of cancer."

They also found that the cancer incidence and risk in unaffected parents of patients with polyQ diseases were similar to those in the general population. This suggests that familial factors, such as shared genetic and environmental factors, "are unlikely to contribute notably to the protective effect," they say.

"On the basis of the similar protective effects across the polyQ diseases studied, these disorders could be reconsidered as a set of hereditary cancer-suppressive diseases," Dr. Ji and colleagues suggest in their report.

They say that the exact underlying mechanisms behind the apparent protective effects of polyQ diseases on cancer are unclear and require further research.

In HD, the tumor-suppressor protein P53 is highly expressed, which could partly explain the decreased risk for cancer. However, no association has been reported between P53 expression and other polyQ diseases, and P53 mutations are found in less than half of all tumors, suggesting, say the researchers, that other mechanisms, such as apoptosis caused by expanded polyQ tracts or altered neurotransmitter release, are involved.

Previous studies have also found decreased risks for cancer in other neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, as well as in schizophrenia. "Whether the protective effects against cancer in polyQ diseases and other neurodegenerative disorders involve similar pathways should also be investigated," the authors say.

The study was funded by the Swedish Cancer Society and the Swedish Council for Working Life and Social Research. The authors have disclosed no relevant financial relationships.

Lancet Oncol. Published online April 12, 2012. Abstract


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