Phenotypic differences in Juvenile Polyposis Syndrome with or without a disease-causing SMAD4/BMPR1A variant

Suzanne P. MacFarland*, Jessica E. Ebrahimzadeh, Kristin Zelley, Lubna Begum, Lee M. Bass, Randall E. Brand, Beth Dudley, Douglas S. Fishman, Amanda Ganzak, Eve Karloski, Alicia Latham, Xavier Llor, Sharon Plon, Mary K. Riordan, Sarah R. Scollon, Zsofia K. Stadler, Sapna Syngal, Chinedu Ukaegbu, Jennifer M. Weiss, Matthew B. YurgelunGarrett M. Brodeur, Petar Mamula, Bryson W. Katona*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Juvenile polyposis syndrome (JPS) is a clinically diagnosed hamartomatous polyposis syndrome that increases the risk of gastrointestinal cancer. Approximately 40%-50% of JPS is caused by a germline disease-causing variant (DCV) in the SMAD4 or BMPR1A genes. The aim of this study was to characterize the phenotype of DCV-negative JPS and compare it with DCV-positive JPS. Herein, we analyzed a cohort of 145 individuals with JPS from nine institutions, including both pediatric and adult centers. Data analyzed included age at diagnosis, family history, cancer history, need for colectomy/ gastrectomy, and polyp number and location. Compared with DCV-positive JPS, DCV-negative JPS was associated with younger age at diagnosis (P < 0.001), lower likelihood of having a family history of JPS (P < 0.001), and a lower risk of colectomy (P=0.032). None of the DCV-negative individuals had gastric or duodenal polyps, and polyp burden decreased after the first decade compared with DCV-positive JPS. Subgroup analysis between SMAD4 and BMPR1A carriers showed that SMAD4 carriers were more likely to have a family history of JPS and required gastrectomy. Taken together, these data provide the largest phenotypic characterization of individuals with DCVnegative JPS to date, showing that this group has distinct differences compared with JPS due to a SMAD4 or BMPR1A variant. Better understanding of phenotype and cancer risk associated with JPS both with and without a DCV may ultimately allow for individualized management of polyposis and cancer risk.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalCancer Prevention Research
Issue number2
StatePublished - Feb 1 2021

ASJC Scopus subject areas

  • Medicine(all)


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