S1428 Occurrence of Gastric Cancer in Patients with Juvenile Polyposis Syndrome: A Systematic Review and Meta-Analysis

Abstract

Introduction: Juvenile polyposis syndrome (JPS) is an autosomal dominant gastrointestinal (GI) polyposis syndrome that affects 1 in 100,000 to 160,000 people. The germline pathogenic variants (PV) in the SMAD4 and BMPR1A genes cause JPS in 60% cases. The syndrome predisposes to hamartomatous GI polyps especially in the colon. It also increases the risk of colonic and gastric cancer. But, due to its rarity, and likely ascertainment bias in published studies, the true rate of gastric cancer in JPS is unknown. Accurate information regarding the risk of gastric cancer may help individualize surveillance endoscopy intervals in these patients. Hence, we conducted a systematic review and meta-analysis to assess the occurrence of gastric cancer in patients with JPS. Methods: We searched Medline, Embase and Scopus databases for keywords ‘Juvenile polyposis syndrome, juvenile polyps, stomach cancer, and hereditary cancers.’ All published studies from January 1974 to May 2021 were screened. The diagnosis of JPS was based on phenotype: >3 colonic juvenile polyps (JP), or multiple JP in other parts of the GI tract or family history of JPS and any number of JP. Studies reporting upper GI manifestations in JPS patients were considered eligible for inclusion. The primary and secondary outcomes were to assess the occurrence of gastric cancer in all patients with JPS and per the underlying PV, respectively. A random-effects model was used. Inter-study heterogeneity was estimated using I2 statistic. Results: Nine studies including 553 patients met our criteria (Table 1). 254 (45.9%) patients had a SMAD4 PV, 154 (27.8%) had BMPR1A PV, 93 (16.8%) had no identifiable PVs and 52 (9.4%) patients were untested. The pooled occurrence of gastric cancer was 4.5% (95% CI: 1.9, 7.1; I2: 35.2%) (Figure 1a). The median age of gastric cancer detection was 42.5 years (range: 29-57.6 years). In studies with no prior genetic testing, gastric cancer occurred in 7.8 % (95% CI: 0,16.3; I2 = 0) patients. In patients with known PVs, gastric cancer was seen only in patients with SMAD4 (11.5%, 95% CI: 3.5, 19.6; I2: 67.1%) (Figure 1b). No gastric cancer was reported in patients with BMPR1A PV those without detectable PV. There was an overall moderate risk of bias in the studies. Conclusion: The risk of gastric cancer is increased in patients with JPS especially in patients with SMAD4 PV. The patients without prior PV testing in the present literature may harbor BMPR1A PV, these patients need to be studied in further large-scale studies.Figure 1.: CONSORT diagram Figure 2. Performance of Model.Table 1.: Characteristics of the included studies Footnotes: *Multicenter studies, †Age at any cancer diagnosis, not specific to gastric cancer, ‡Included patients from the same family, §13 patients were not tested for pathogenic variants, none of these patients developed gastric cancer. **The risk of bias of individual studies was assessed using the validated criteria by Hoy et al. Abbreviations: JPS: Juvenile Polyposis syndrome, PV: Pathogenic variants, NR: Not reported.