Abstract
INTRODUCTION: Families with pathogenic germline variants (pv) in BRCA1/2 may have besides breast and ovarian cancer an elevated lifetime risk for other cancer types. MATERIAL AND METHODS: Data and pedigree information from 1852 family members of 286 BRCA1/2 positive families were analyzed. Genetic testing was conducted between 2015 and 2017 at the HBOC center at Charité - Universitätsmedizin Berlin. Relative cancer risk (RR) was calculated by comparing observed cancer incidence with the expected incidence in the German population. RESULTS: BRCA1/2 positive families showed an elevated cancer risk for gastric and cervical cancer regardless of BRCA status. The relative risk of gastric cancer was higher in BRCA2 carriers compared to BRCA1 carriers (gBRCA1 RR 1.42; 95% CI: 0.65-2.69 vs. gBRCA2 RR 1.88; 95% CI: 0.75-3.87). Similarly, the relative risk for cervical cancer was also greater in BRCA2 carriers than in BRCA1 carriers (gBRCA1 RR 1.88; 95% CI: 0.69-4.09 vs. gBRCA2 RR 2.09; 95% CI: 0.56-5.35). Additionally, BRCA2 families showed an increased risk of pancreatic cancer (RR 1.56; 95% CI, 0.50 to 3.63). No significant associations were found for other cancer entities. CONCLUSION: In the present study, an increased risk of gastrointestinal cancer was observed in German families with pathogenic BRCA1/2 variants, consistent with findings from previous research. Potential new associations with cervical cancer were also identified, warranting confirmation through large prospective studies. These findings highlight the importance of developing additional screening programs or preventive strategies for BRCA carriers, especially with regard to upper gastrointestinal tract malignancies.