Unusual features of thyroid carcinomas in Japanese patients with Werner syndrome and possible genotype-phenotype relations to cell type and race

BACKGROUND. Werner syndrome (WS), an autosomal recessive disease characteri zed by premature aging, has a high frequency of association with six rare n eoplasms in Japanese patients, and only four of these neoplasms also occur excessively in whites. Several differ from what is usual in their epidemiol ogy and/or histology. Described in this article are peculiarities in the oc currences of follicular and papillary thyroid carcinomas among Japanese pat ients and the possible genotype-phenotype relations pertaining to cell type s and the absence of excess thyroid carcinoma occurrence in whites with WS. METHODS. Epidemiologic features of 23 histologically diagnosed thyroid carc inomas from a series of 150 cancers in 845 Japanese patients with WS were c ompared with those of 19,446 tumors in a Japanese national registry of thyr oid carcinomas from 1977-1991. Germline mutations had been determined by mo lecular studies of peripheral blood. RESULTS. The average age of patients with thyroid carcinoma was 39 years fo r those with WS and 49 years for the registry patients. The female-to-male ratios were 2.3 : 1 and 6.6 : 1, respectively. The rates of occurrence-of p apillary, follicular, and anaplastic carcinomas were 35%, 48%, and 13% for Japanese patients with WS and 78%, 14%, and 2% in the general Japanese popu lation. AU four cases of follicular carcinoma had germline mutations of the WS gene in the C-terminal region, and the germline mutation for the only p apillary carcinoma was in the N-terminal region. CONCLUSIONS. This study suggests two possible WS genotype-phenotype relatio ns. One concerns thyroid carcinoma histology; the other concerns frequent m utations that occur in the C-terminal region in Japanese patients, but not in white patients, with WS. These may account for the excess thyroid carcin oma occurrence among Japanese. Cancer 1999;85:1345-52. (C) 1999 American Ca ncer Society.