Cancer incidence in patients with polyglutamine diseases: a population-based study in Sweden

Lancet Oncol. 2012 Jun;13(6):642-8. doi: 10.1016/S1470-2045(12)70132-8. Epub 2012 Apr 12.


Background: Polyglutamine (polyQ) diseases are characterised by the expansion of CAG triplet repeats in specific genes. The accumulated encoded proteins affect the transcription of numerous transcription factors. We investigated whether polyQ diseases reduce the risk of cancer development.

Methods: Data on patients with the polyQ diseases Huntington's disease (HD), spinobulbar muscular atrophy (SBMA), and hereditary ataxia (HA) in Sweden were linked to the Swedish Cancer Registry. We calculated standardised incidence ratios for cancers at specific sites or of specific types and the risks were compared with those in the general population. We also analysed risks in the unaffected parents of patients.

Findings: In the period January, 1969, to December, 2008, we identified 1510 patients with HD, 471 with SBMA, and 3425 with HA. Cancer was diagnosed in 91 (6·0%) HD patients, 34 (7·2%) SBMA patients, and 421 (12·3%) HA patients. The standardised incidence ratios were 0·47 (95% CI 0·38-0·58), 0·65 (0·45-0·91), and 0·77 (0·70-0·85), respectively. Before diagnosis of polyQ disease, the risk of cancer was even lower. Cancer incidence and risk in the unaffected parents of patients with polyQ diseases were similar to those in the general population.

Interpretation: The consistently decreased incidence of cancer in patients with polyQ diseases suggests that a common mechanism protects against the development of cancer. This feature could be related to the polyQ-tract expansion seen in these diseases. Further studies are warranted to investigate the underlying mechanisms linking cancer and polyQ diseases.

Funding: Swedish Cancer Society, Swedish Council for Working Life and Social Research.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Databases, Factual
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / epidemiology*
  • Neoplasms / genetics*
  • Neoplasms / physiopathology
  • Neurodegenerative Diseases / epidemiology*
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / physiopathology
  • Peptides / genetics*
  • Peptides / metabolism
  • Registries
  • Retrospective Studies
  • Risk Assessment
  • Sex Distribution
  • Survival Analysis
  • Sweden / epidemiology


  • Peptides
  • polyglutamine