Frequency of Positive Familial Criteria in Patients with Adenocarcinoma of the Esophageal-Gastric Junction and Stomach: First Prospective Data in a Caucasian Cohort †

SIMPLE SUMMARY: It is well known for gastric cancer patients with subtype of diffuse histology that a proportion of patients harbour an increased familial risk. Some patients and relatives even may be detected through a genetic testing. More precise studies about the frequency of hereditary criteria in a poplation with only European ancestries for adenocarcinoma of the esophagogastric junction and stomach are missing. In current guidelines regarding genetic testing criteria not all types of stomach cancer are considered as for example patients not with subtype of diffuse histology mostly have no detectable responsible gene. The aim of the current study was to register stomach cancer patients of all different types in a certain region (Berlin, Germany) and to estimate the frequency of positive familial criteria. Patients with esophageal cancer served as comparison group as familial or hereditary background, respectively, is not significant in these patients according to current knowledge. In our study, we identified positive familial criteria in about 15% of stomach cancer patients. In regard to all different types of stomach cancer, this number almost doubled. Furthermore, one third of all registered patients in this study might have a familial or hereditary background of their disease. We therefore conclude that guidelines regarding genetic testing criteria and screening examinations should be adjusted in future. ABSTRACT: Objectives: Current prospective studies investigating the frequency of hereditary criteria in a Caucasian population for adenocarcinoma of the esophagogastric junction (AEG) and stomach (GC) are missing. Genetic testing criteria (screening criteria) for hereditary diffuse gastric cancer (HDGC) were updated in 2020, but do not address patients with intestinal histology (familial intestinal gastric cancer FIGC). Thus, we prospectively screened patients residing in Berlin newly diagnosed with AEG or GC for hereditary criteria to gain insights into the frequency of HDGC. Methods: Prospective documentation of familial/clinical parameters in patients residing in Berlin with AEG or GC over three years was conducted. Besides HDGC criteria from 2015 and revised 2020, we also documented patients fulfilling these criteria but with intestinal type gastric cancer (FIGC). Statistical analysis was performed using X2-test. Results: One hundred fifty-three patients were finally included (92 GC; male: 50 (n.s.); 61 AEG; male: 47; p = 0.007). Hereditary criteria for HDGC were detected in 9/92 (9.8%) (2015 criteria) and in 14/92 (15.2%) (2020 criteria) of GC patients (AEG: 2015 criteria 3/61 (4.9%) versus 4/61 according to 2020 criteria (6.5%)). Patients fulfilling hereditary criteria but with intestinal histology (FIGC) increased from 8.7% (2015) to 14.1%, respectively (2020) (AEG: 3.2% (2015) versus 6.6% (2020)). Hereditary criteria including intestinal histology were found in 29.3% (GC) and 13.1% (AEG) (p = 0.03) according to the 2020 criteria. Conclusions: HDGC criteria were found in 15.2% of GC patients according to the 2020 criteria. Percentage increased to 29.3% including patients with intestinal histology among the GC group, and was 13.1% in cases with AEG. These data indicate that family history seems to be of utmost importance in GC to further detect potential hereditary genetic risks. This equally applies for patients with intestinal subtype GC.