Phenotypic Differences in Juvenile Polyposis Syndrome With or Without a Disease-causing SMAD4/BMPR1A Variant.
Cancer Prev Res (Phila)
; 14(2): 215-222, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-33097490
ABSTRACT
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 DCV-negative 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.Prevention Relevance 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 SMAD4 or BMPR1A 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Syndromes, Hereditary
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Colectomy
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Intestinal Polyposis
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Bone Morphogenetic Protein Receptors, Type I
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Smad4 Protein
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Watchful Waiting
Type of study:
Diagnostic_studies
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Guideline
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Adolescent
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Adult
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Aged
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Cancer Prev Res (Phila)
Journal subject:
NEOPLASIAS
Year:
2021
Document type:
Article