Is Juvenile Polyposis Syndrome Associated With a Significant Risk of Gastric Cancer?

Is Juvenile Polyposis Syndrome Associated With a Significant Risk of Gastric Cancer?

Vanessa M. Shami, MD, FASGE, reviewing Singh AD, et al. Gastrointest Endosc 2022 Oct 17.

Juvenile polyposis syndrome (JPS), in which patients develop juvenile polyps, is uncommon but is thought to be associated with an increased risk of gastrointestinal cancers. About 60% of patients with JPS have pathogenic germline variants (PGVs) in SMAD4 and BMPR1A, whereas 40% have no evident PGVs. The primary outcome of this systemic review and meta-analysis was to investigate the reported incidence of gastric cancer (GC) in JPS. The secondary outcome was to study the occurrence of GC in tested patients with or without PGVs as well as in patients who had not undergone germline genetic testing. 

The study of patients with JPS included 637 participants with a median age of 42.5 years (range, 15-57.6). The pooled occurrence of GC was 3.5% (95% confidence interval [CI], 1.8%-5.2%; I2, 12.3%). Patients with SMAD4 PGV had a pooled GC occurrence of 10.1% (95% CI, 3.2%-16.8%; I2, 54.7%). In patients without identifiable PGVs, there were no incidents of GC reported. In SMAD4 PGV carriers, the risk of GC was higher (odds ratio, 11.6; 95% CI, 4.6%-29.4%; I2, 18.3%) compared with patients without SMAD4 PGV. Only one patient who was a carrier for BMPR1A PGV had GC. In patients with JPS whose germline testing status was unknown, the pooled occurrence of GC was 7.5% (95% CI, 0%-15.5%).

Vanessa M. Shami, MD, FASGE


SMAD4 PGV in patients with JPS appears to increase the risk of GC, whereas its absence does not. Perhaps the decision to survey patients with JPS for gastric cancer will be based on the absence or presence of SMAD4 PGV, suggesting that germline testing should be performed in these patients.  

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.


Singh AD, Gupta A, Mehta N, et al. Occurrence of gastric cancer in patients with juvenile polyposis syndrome: a systematic review and meta-analysis. Gastrointest Endosc 2022 Oct 17. (Epub ahead of print) (

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