Spectrum and risk of neoplasia in Werner syndrome

Abstract

Background: Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid syndrome that is associated with an elevated risk of cancer. Methods: We used case reports of neoplasms in WS patients identified in previous case series or newly identified through searches of PubMed, Google Scholar and J-EAST (a database of articles from Japan) to define the spectrum (types and sites) of neoplasia in WS. Neoplasm type-specific risk was calculated by determining standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively) of neoplasms in Japan-resident WS patients versus population control data from the Osaka prefecture and Osaka Cancer Registry. Results: Our study population consisted of 188 WS patients with 246 neoplasms. 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. SIRs were significantly elevated in Japanese WS patients for the five most frequent cancer types and meningiomas, from 83.2-fold for melanomas of the skin (95% CI: 45.5, 139.6) to 3.6-fold for leukemias (95% CI: 1.7, 6.9), and for all five cancer types except leukemias by SPIR analysis. Conclusions: WS confers a strong predisposition to several specific types of neoplasia, and this spectrum differs between WS patients residing in, as opposed to outside, Japan. These results provide a guide for WS clinical care and cancer screening, and for analyses to define the mechanistic basis for cancer in WS and in the general population.