Phenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4 / BMPR1A Variant

• Published in: Cancer prevention research (Philadelphia, Pa.) Pa.), 2021-02, Vol.14 (2), p.215-222
• Main Authors: MacFarland, Suzanne P, Ebrahimzadeh, Jessica E, Zelley, Kristin, Begum, Lubna, Bass, Lee M, Brand, Randall E, Dudley, Beth, Fishman, Douglas S, Ganzak, Amanda, Karloski, Eve, Latham, Alicia, Llor, Xavier, Plon, Sharon, Riordan, Mary K, Scollon, Sarah R, Stadler, Zsofia K, Syngal, Sapna, Ukaegbu, Chinedu, Weiss, Jennifer M, Yurgelun, Matthew B, Brodeur, Garrett M, Mamula, Petar, Katona, Bryson W
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Aged; Bone Morphogenetic Protein Receptors, Type I - genetics; Child; Child, Preschool; Colectomy - standards; Colectomy - statistics & numerical data; Colonoscopy - standards; Colonoscopy - statistics & numerical data; Female; Follow-Up Studies; Germ-Line Mutation; Humans; Intestinal Polyposis - congenital; Intestinal Polyposis - diagnosis; Intestinal Polyposis - genetics; Intestinal Polyposis - therapy; Male; Medical History Taking - statistics & numerical data; Middle Aged; Neoplastic Syndromes, Hereditary - diagnosis; Neoplastic Syndromes, Hereditary - genetics; Neoplastic Syndromes, Hereditary - therapy; Practice Guidelines as Topic; Precision Medicine - methods; Precision Medicine - statistics & numerical data; Smad4 Protein - genetics; Watchful Waiting - standards; Watchful Waiting - statistics & numerical data; Young Adult
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.CAPR-20-0348

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 or 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 ( < 0.001), lower likelihood of having a family history of JPS ( < 0.001), and a lower risk of colectomy ( = 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 and carriers showed that 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 DCV-negative JPS to date, showing that this group has distinct differences compared with JPS due to a or 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. Juvenile Polyposis Syndrome (JPS) is a gastrointestinal cancer predisposition syndrome requiring lifelong surveillance, however there is limited data comparing individuals with and without a germline disease-causing variant in or Herein we show that individuals with JPS without an underlying disease-causing variant have distinct phenotypic differences including lack of upper gastrointestinal polyps and lower rates of a family history of JPS, suggesting that a different approach to management may be appropriate in this population.