Prevalence of <scp> <i>Helicobacter pylori</i> </scp> Exposure and Risk Factors Among <scp> <i>BRCA1</i> </scp> and <scp> <i>BRCA2</i> </scp> Carriers

ABSTRACT Recent evidence suggests that carriers of a pathogenic germline variant (PGV) in BRCA1 or BRCA2 may have an increased risk of gastric cancer (GC). However, the specific mechanisms underlying gastric carcinogenesis remain uncertain. Strikingly, recent data have demonstrated that Japanese BRCA1 and BRCA2 PGV carriers with Helicobacter pylori ( Hp ) exposure have a substantially increased risk of GC compared to non‐carriers with Hp exposure, indicating that Hp may be an important risk factor for BRCA1 and BRCA2 ‐associated GC. However, rates of Hp exposure amongst broader BRCA1 and BRCA2 PGV cohorts are currently unknown. In this study, 1034 United States‐based BRCA1 and BRCA2 PGV carriers along with 293 PALB2 , ATM , and TP53 PGV carriers were assessed for Hp exposure by assessing Hp IgG positivity in plasma samples. The combined rate of Hp exposure in BRCA1 and BRCA2 carriers was 17.4%. Individually, BRCA1 and BRCA2 carriers had an exposure rate of 16.4% and 18.2%, respectively. Similarly, PALB2 , ATM , and TP53 carriers had a combined Hp exposure rate of 18.4%. Among all groups, non‐White race was significantly associated with Hp exposure. Approximately 1 in 6 BRCA1 , BRCA2 , and other DNA repair‐related gene PGV carriers had Hp exposure. Future studies are needed to determine the impact of Hp exposure versus active Hp infection on GC risk in these high‐risk individuals.