Background: Although hereditary diffuse gastric cancer syndrome is a rare condition its contribution to gastric cancer burden in Brazil is unknown. The aim of this study was to examine the frequency of CDH1 germline mutations in a population-based series of diffuse gastric cancer (DGC) in Brazil, which is considered a middle/high-incidence country for gastric cancer. Methods: From October 2013 to October 2014 a total of 64 unrelated and consecutive patients attending a Brazilian public hospital with DGC were enrolled and all CDH1 exons and intronic boundaries were sequenced. Clinico-pathological features were extracted from electronic medical records. Recruitment for this study is still ongoing. Results: Of 64 patients, 57.8% were female and the mean age at gastric cancer diagnosis was 46.6 years (range 21-76); 17% reported family history of gastric cancer in first- or second-degree relatives, 39% were diagnosed ≤ 40 years old, and none of them fulfilled the original 1999 International Gastric Cancer Linkage Consortium criteria for genetic testing. The majority of the tumors were poorly differentiated (84%), and located in the middle and distal-third of the stomach (70%). One germline deleterious mutation (c.1849G>A, p.A617T) was identified in 2 unrelated female patients with DGC (42 years and 47 years) and without family history of gastric cancer (Table 1). The overall frequency of germline CDH1 mutations was 3.1% (2/64) for DGC. Conclusions: To our knowledge, this is the largest population-based study investigating the contribution of CDH1 germline mutations in DGC cancer in Brazil. For a middle/high-incidence country, mutation frequency was higher than expected. This finding warrants further validation in larger cohort studies.

Abbreviations: F, female; Hp, Helicobacter pylori; Fam hist, family history of gastric cancer in first- or second-degree relatives; N/A, not available; yo, years old.