TY - JOUR
T1 - Phenotypic differences in Juvenile Polyposis Syndrome with or without a disease-causing SMAD4/BMPR1A variant
AU - MacFarland, Suzanne P.
AU - Ebrahimzadeh, Jessica E.
AU - Zelley, Kristin
AU - Begum, Lubna
AU - Bass, Lee M.
AU - Brand, Randall E.
AU - Dudley, Beth
AU - Fishman, Douglas S.
AU - Ganzak, Amanda
AU - Karloski, Eve
AU - Latham, Alicia
AU - Llor, Xavier
AU - Plon, Sharon
AU - Riordan, Mary K.
AU - Scollon, Sarah R.
AU - Stadler, Zsofia K.
AU - Syngal, Sapna
AU - Ukaegbu, Chinedu
AU - Weiss, Jennifer M.
AU - Yurgelun, Matthew B.
AU - Brodeur, Garrett M.
AU - Mamula, Petar
AU - Katona, Bryson W.
N1 - Funding Information:
This work was supported by the Precious Jules Foundation (to S.P. MacFarland), Alex's Lemonade Stand Foundation (to S.P. MacFarland), The Donaldson Fund (to M.B. Yurgelun, S. Syngal, and C. Ukaegbu), the NIH (K08DK106489 and R03DK120946 to B.W. Katona), and the Lustgarten Family Colon Cancer Research Fund (to B.W. Katona).
Funding Information:
This work was supported by the Precious Jules Foundation (to S.P. MacFarland), Alex’s Lemonade Stand Foundation (to S.P. MacFarland), The Donaldson Fund (to M.B. Yurgelun, S. Syngal, and C. Ukaegbu), the NIH (K08DK106489 and R03DK120946 to B.W. Katona), and the Lust-garten Family Colon Cancer Research Fund (to B.W. Katona).
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1940-6207.CAPR-20-0348
DO - 10.1158/1940-6207.CAPR-20-0348
M3 - Article
C2 - 33097490
AN - SCOPUS:85100583040
SN - 1940-6207
VL - 14
SP - 215
EP - 222
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 2
ER -
