Spectrum and Risk of Neoplasia in Werner Syndrome: A Systematic Review

PLoS One. 2013;8(4):e59709. doi: 10.1371/journal.pone.0059709. Epub 2013 Apr 1.


Background: Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid ('premature aging') syndrome which is associated with an elevated risk of cancer.

Objectives: Our study objectives were to characterize the spectrum of neoplasia in WS using a well-documented study population, and to estimate the type-specific risk of neoplasia in WS relative to the general population.

Methods: We obtained case reports of neoplasms in WS patients through examining previous case series and reviews of WS, as well as through database searching in PubMed, Google Scholar, and J-EAST, a search engine for articles from Japan. We defined the spectrum (types and sites) of neoplasia in WS using all case reports, and were able to determine neoplasm type-specific risk in Japan WS patients by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively) relative to Osaka Japan prefecture incidence rates.

Results: We used a newly assembled study population of 189 WS patients with 248 neoplasms to define the spectrum of neoplasia in WS. The most frequent neoplasms in WS patients, representing 2/3 of all reports, were thyroid neoplasms, malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, and primary bone neoplasms. Cancer risk defined by SIRs was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia, ranging from 53.5-fold for melanoma of the skin (95% CI: 24.5, 101.6) to 8.9 (95% CI: 4.9, 15.0) for thyroid neoplasms. Cancer risk as defined by SPIR was also significantly elevated for the most common malignancies except leukemia.

Conclusions: WS confers a strong predisposition to several specific types of neoplasia. These results serve as a guide for WS clinical care, and for additional analyses to define the mechanistic basis for cancer in WS and the general population.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Humans
  • Incidence
  • Japan / epidemiology
  • Neoplasms / epidemiology
  • Neoplasms / etiology*
  • Risk
  • Werner Syndrome / complications*
  • Werner Syndrome / epidemiology