New York-Presbyterian/Weill Cornell Medical Center New York, NY
Ariel Bar-Mashiah, MD, Soham Sinha, MS, Zixuan Li, MS, Ravi Sharaf, MD New York-Presbyterian/Weill Cornell Medical Center, New York, NY
Introduction: Approximately 10% of gastric cancers result from monogenic germline predisposition. The aim of this study was to determine gastric cancer risk in specific hereditary cancer syndromes.
Methods: A systematic literature review was conducted using the GRADE methodology. A literature search was conducted in MEDLINE (PubMed), Embase, and Cochrane from June 2016 through November 2021. Inclusion criteria were articles that detailed gastric cancer risk estimates in patients with Hereditary Diffuse Gastric Cancer (HDGC) (CDH1 mutation), Lynch Syndrome (LS) (MLH1, MSH2, PMS2, MSH6 mutations), Familial Adenomatous Polyposis (FAP) (APC mutation) and germline mutations in BRCA 1, BRCA 2, CTNNA1, MUTYH, SMAD4, BMPR1A, TP53, STK11, ATM, PALB2, and PRSS1. Two reviewers independently evaluated titles and abstracts for relevance and obtained text of potentially eligible articles, and determined final eligibility after full text review. Data was reported qualitatively given heterogeneity in available literature that precluded quantitative comparison.
Results: The literature search revealed 2,494 observational studies, of which 26 met inclusion criteria for full-text abstraction. For HDGC, ranges for cumulative incidence of diffuse gastric cancer (DGC) varied widely across four studies. In men, four studies showed cumulative incidence by the eighth decade of life ranged from 37.2% (95% CI, 8.7-89.5) to 70.0% (95% CI, 40-94), while ranges for women were uniformly lower by the eighth decade, ranging from 24.7% (95% CI 6.1-68.9) to 63% (95% CI 19-99). Three studies found RR of gastric cancer in BRCA1/2 carriers ranged from 2.59 (95% CI, 1.46-4.61) to 6.2 (95% CI 2.0-19). Across all genetic mutations associated with LS, eight studies reported the cumulative incidence of gastric cancer to age 70 of 2.0% to 14.7%, with a higher incidence in MLH1 carriers compared to MSH2 and MSH6.
Discussion: The gastric cancer risk for hereditary cancer syndromes is not well described. In HDGC carriers, gastric cancer risk estimates vary widely across studies. Among individuals with LS, cumulative risk varied widely with a peak lifetime risk estimate of 14.7% and the highest lifetime risk in MLH1 carriers compared to MSH2 and MSH6 carriers. Prospective large population-based cohort studies are needed in order to accurately determine the gastric cancer risk in hereditary cancer syndromes.
Disclosures:
Ariel Bar-Mashiah indicated no relevant financial relationships.
Soham Sinha indicated no relevant financial relationships.
Zixuan Li indicated no relevant financial relationships.
Ravi Sharaf indicated no relevant financial relationships.
Ariel Bar-Mashiah, MD, Soham Sinha, MS, Zixuan Li, MS, Ravi Sharaf, MD. A0692 - Gastric Cancer Risk Estimates in Hereditary Cancer Syndromes: A Systematic Review, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.
