Frequency of CDH1 Germline Mutations in Diffuse Gastric Cancer in Brazil.

e12535 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. Clinical characteristics of CDH1 mutation carriers. Age Sex Stage Part Grade Mucinous Hp Fam hist 42 yo F IV body Poorly differentiated yes N/A no 47 yo F IIb pylorus Poorly differentiated no positive no 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.