Risk of malignant paraganglioma in SDHB-mutation and SDHD-mutation carriers: a systematic review and meta-analysis

J Med Genet. 2012 Dec;49(12):768-76. doi: 10.1136/jmedgenet-2012-101192. Epub 2012 Oct 25.

Abstract

The main objective of this study was to perform a systematic review and meta-analysis on the risk of developing malignant paraganglioma (PGL) in SDHB-mutation and SDHD-mutation carriers. PubMed, EMBASE, Web of Science, COCHRANE and Academic Search Premier (2000-August 2011) and references of key articles were searched to identify potentially relevant studies. The main outcomes were the pooled incidence and prevalence of malignant PGL in SDHB-mutation and SDHD-mutation carriers. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Twelve studies were included. The pooled incidence of malignant PGL in populations comprising both asymptomatic mutation carriers and mutation carriers with manifest non-malignant PGL was 17% (95% CI 10 to 28) for SDHB-mutation carriers and 8% (95% CI 2 to 26) for SDHD-mutation carriers. The pooled risk in prevalence studies was 13% (95% CI 4 to 34) and 4% (95% CI 2 to 7), respectively. In studies comprising only mutation carriers with manifest disease, the pooled prevalence was 23% (95% CI 16 to 33) for SDHB-mutation and 3% (95% CI 1 to 10) for SDHD-mutation carriers. Incidence and prevalence of malignant PGL are higher in SDHB-mutation than in SDHD-mutation carriers, but lower in SDHB-mutation carriers than hitherto appreciated.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Genetic Predisposition to Disease*
  • Genotype*
  • Humans
  • Incidence
  • Mutation*
  • Paraganglioma / epidemiology
  • Paraganglioma / genetics*
  • Prevalence
  • Risk
  • Succinate Dehydrogenase / genetics*

Substances

  • SDHD protein, human
  • SDHB protein, human
  • Succinate Dehydrogenase