Chinese Multicenter Registry for Peutz-Jeghers Syndrome
This prospective, observational patient registry will enroll approximately 1,000 individuals with a clinical or molecular diagnosis of Peutz-Jeghers syndrome (PJS) at participating hospitals in China. The registry will collect standardized clinical information, existing genetic test reports, family history, and longitudinal outcomes. The primary objective is to estimate the 10-year cumulative incidence of a first invasive malignancy after enrollment among participants without a previous malignancy or an unresolved suspected malignancy at baseline, accounting for death as a competing event. Secondary objectives address organ-specific malignancies, new primary cancers in participants with a cancer history, mortality, major polyp-related complications, and clinical and STK11 variant characteristics. Participants may be followed for up to 20 years. Biospecimen donation, additional baseline sampling, research sequencing, and patient-derived organoid studies are optional and require the corresponding consent. Refusal of an optional component does not preclude participation in the clinical registry. No treatment or clinical surveillance strategy is assigned by the study.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
Peutz-Jeghers syndrome is a rare inherited tumor-predisposition syndrome associated with gastrointestinal hamartomatous polyps, mucocutaneous pigmentation, and increased risks of several malignancies. This multicenter registry will document the clinical course of enrolled patients receiving usual care and will support carefully defined genotype-phenotype and translational research. It is a hospital-based, non-probability sample and is not designed to provide a probability-representative estimate for the entire Chinese PJS population.
The purpose of this study is to establish a nationwide multicenter registry of patients with PJS, integrating standardized clinical information, existing genetic reports, optional biospecimen studies and prospective follow-up. The primary objective is to estimate 10-year cumulative incidence of a first invasive malignancy among participants without previous or unresolved suspected malignancy at baseline. The study will support defined genotype-phenotype and translational analyses; it does not assign treatment or clinical surveillance.
Specific study objectives are listed below:
- Establish a standardized PJS clinical database to define the clinical characteristics and natural history of the disease in Chinese patients.
- Analyze the landscape of STK11 gene variants and the relationship between genotype and clinical phenotype.
- Establish an optional biobank of patients with PJS, using separately consented specimens, to provide resources for approved research.
- Establish separately consented patient-derived organoid models to investigate disease mechanisms and in vitro drug responses without directing patient treatment.
- Explore the development of a precision management system. The workflow includes consecutive recruitment, diagnostic confirmation, core registry consent, baseline clinical-data abstraction, prospective follow-up and outcome review. Biospecimen collection, research sequencing and organoid studies are optional components; refusal does not preclude enrollment.
The registry will implement standardized baseline clinical-data abstraction, prospective follow-up and outcome review, with historical medical information will be abstracted at baseline and distinguished from prospectively observed events. All eligible, consenting participants contribute to the clinical registry. Participants will be contacted approximately every 12 months through routine visits, telephone, or institution-approved remote methods. Clinical and genetic associations will account for family relationships, recruitment pathway, center, and relevant prespecified covariates. STK11 germline variants will be classified using the ACMG/AMP framework and applicable subsequent guidance, with the reference sequence, testing scope, evidence, and interpretation date documented. Germline and tumor-only findings will be distinguished. Untested participants, participants with limited testing, those with variants of uncertain significance, and those with adequately evaluated negative findings will not be combined into a single wild-type group.
The primary analysis will estimate the cumulative incidence function at 10 years using an Aalen-Johansen approach, with uncertainty accounting for family clustering when supported by the data. Attained-age analyses will use delayed entry at enrollment and will not treat the period before enrollment as prospectively observed person-time. Optional biospecimen studies prioritize clinical residual material. No research-only tissue biopsy or enlargement of a clinical resection is permitted.Research sequencing, multi-omics, and patient-derived organoid or tumor-organoid studies will be performed only in authorized, suitable subsets. Laboratory and analytical methods will distinguish biological participants from repeated specimens or culture wells. Predictive biomarker analyses require pre-outcome specimens and family-separated validation. Research findings will not direct clinical treatment; clinically meaningful findings considered for return require appropriate confirmation, counseling, and the participant's documented preference.
Undersøgelsestype
Tilmelding (Anslået)
Kontakter og lokationer
Studiekontakt
- Navn: Yu Kang
- Telefonnummer: +86 19560161853
- E-mail: kangyu@hospital.westlake.edu.cn
Studiesteder
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Beijing, Kina
- Ikke rekrutterer endnu
- Peking University Third Hospital
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Kontakt:
- Congrong Liu
- Telefonnummer: +86 13651215671
- E-mail: congrong_liu@163.com
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Shanghai, Kina
- Ikke rekrutterer endnu
- Fudan University Shanghai Cancer Center
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Kontakt:
- Yanyun Li
- Telefonnummer: +86 13601903229
- E-mail: liyanyun@fudan.edu.cn
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Shanghai, Kina
- Ikke rekrutterer endnu
- Obstetrics & Gynecology Hospital of Fudan University
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Kontakt:
- Jing Xu
- Telefonnummer: +86 18817301819
- E-mail: doctor_xj@163.com
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Tianjin, Kina
- Ikke rekrutterer endnu
- The Second Hospital of Tianjin Medical University
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Kontakt:
- Haitao Wang
- Telefonnummer: +86 18630955984
- E-mail: peterrock2000@126.com
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Fujian
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Fuzhou, Fujian, Kina
- Ikke rekrutterer endnu
- Fujian Maternity and Child Health Care Hospital
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Kontakt:
- Huan Yi
- Telefonnummer: +86 15960103922
- E-mail: yi.huan@fjmu.edu.cn
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Guangdong
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Guangzhou, Guangdong, Kina
- Ikke rekrutterer endnu
- Sun Yat-sen University Cancer Center
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Kontakt:
- Yanling Feng
- Telefonnummer: +86 13925090579
- E-mail: fengyl@sysucc.org.cn
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Shandong
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Jinan, Shandong, Kina
- Ikke rekrutterer endnu
- Qilu Hospital of Shandong University
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Kontakt:
- Peng Li
- Telefonnummer: +86 18560082010
- E-mail: peng_li2002@163.com
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Zhejiang
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Hangzhou, Zhejiang, Kina
- Rekruttering
- First People's Hospital of Hangzhou
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Kontakt:
- Yu Kang
- Telefonnummer: +86 19560161853
- E-mail: kangyu@hospital.westlake.edu.cn
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Hangzhou, Zhejiang, Kina
- Ikke rekrutterer endnu
- Zhejiang Cancer Hospital
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Kontakt:
- Qiang Wen
- Telefonnummer: +86 13857105097
- E-mail: wenqiang@zjcc.org.cn
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Individuals with a confirmed clinical or molecular diagnosis of PJS who receive care at participating centers in China. Recruitment will be consecutive where feasible. Previous cancer does not preclude registry enrollment. Diagnostically unconfirmed relatives are not independently enrolled under this version. Relatives who independently meet clinical or molecular diagnostic criteria may enroll with separate consent and a unique individual identifier linked to a pedigree.
Beskrivelse
Inclusion Criteria:
- A clinical diagnosis of PJS meeting at least one of the following: two or more histologically confirmed Peutz-Jeghers polyps; any number of Peutz-Jeghers polyps and a family history of PJS; characteristic mucocutaneous pigmentation and a family history of PJS; or any number of Peutz-Jeghers polyps together with characteristic mucocutaneous pigmentation. Alternatively, a molecular diagnosis established by a confirmed germline pathogenic or likely pathogenic STK11 variant associated with PJS, interpreted by appropriately qualified professionals.
- Valid written informed consent for the core clinical registry from the participant or the legally appropriate guardian, with age- and capacity-appropriate information and assent when applicable.
- Minimum clinical or genetic documentation sufficient to confirm eligibility and agreement to at least one feasible method of longitudinal contact or record-based follow-up within the approved consent.
Biospecimen donation, availability of all specimen types, and participation in research sequencing or organoid experiments are not required for clinical registry enrollment.
Exclusion Criteria:
- Neither the clinical nor molecular diagnostic pathway can be confirmed. A variant of uncertain significance alone does not satisfy molecular eligibility.
- Absence of valid consent for the core registry. Duplicate records of the same individual will be merged rather than counted as additional participants. Inability or refusal to undergo an optional sample procedure is not a registry exclusion criterion. Procedure-specific safety restrictions affect that procedure only.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: COHORT
- Tidsperspektiver: PROSPECTIVE
Kohorter og interventioner
Gruppe / kohorte |
|---|
|
Peutz-Jeghers syndrome
Individuals meeting protocol-defined clinical diagnostic criteria or carrying a confirmed germline pathogenic or likely pathogenic STK11 variant associated with PJS. Participants with and without previous cancer may enroll. Optional biospecimen and genetic components do not determine clinical registry eligibility. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
10-year cumulative incidence of a first invasive malignancy
Tidsramme: From enrollment to 10 years after enrollment, first invasive malignancy, death, withdrawal, or last reliable event-free assessment, as applicable.
|
Time from registry enrollment to the first confirmed invasive malignant neoplasm among participants with no previous malignancy and no unresolved suspected malignancy at baseline. Pathology will be the preferred evidence for solid tumors; hematologic malignancies will follow the relevant diagnostic criteria. Benign lesions, in situ disease, recurrence, progression, and metastases from an existing primary are excluded from this endpoint. The cumulative incidence at 10 years will be estimated with death before malignancy as a competing event. Participants with previous malignancy are not included in this primary risk set. |
From enrollment to 10 years after enrollment, first invasive malignancy, death, withdrawal, or last reliable event-free assessment, as applicable.
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Organ-specific cumulative incidence of a new primary invasive malignancy
Tidsramme: From enrollment up to 20 years; estimates at 5, 10, and 20 years where supported.
|
First new primary invasive malignancy at each specified organ site, analyzed separately among participants without a previous malignancy at that site and with the relevant organ at risk at baseline. Site and histologic type will be recorded. Death and removal of the at-risk organ without target cancer will be handled according to the prespecified competing-risk or multistate analysis. In situ disease and metastases will not be counted as new primary invasive cancers. |
From enrollment up to 20 years; estimates at 5, 10, and 20 years where supported.
|
|
Cumulative incidence of a subsequent new primary invasive malignancy in participants with a cancer history
Tidsramme: From enrollment up to 20 years.
|
Time from enrollment to the next confirmed new primary invasive malignancy among participants with a malignancy diagnosed before enrollment. New primary disease will be distinguished by clinical review from recurrence, progression, and metastasis of an existing cancer. Death before a subsequent primary cancer is a competing event. |
From enrollment up to 20 years.
|
|
All-cause mortality
Tidsramme: From enrollment up to 20 years; summaries at 5, 10, and 20 years where supported.
|
Time from enrollment to death from any cause among all enrolled participants. Death dates and evidence sources will be recorded. Participants not known to have died will be censored at the last date on which they were known to be alive or the applicable end of follow-up. Survival probabilities and death rates will be reported. |
From enrollment up to 20 years; summaries at 5, 10, and 20 years where supported.
|
|
Cumulative incidence of cancer-related death
Tidsramme: From enrollment up to 20 years.
|
Time from enrollment to death attributed to malignancy, based on available medical records, death documentation, and outcome review. Non-cancer death is a competing event. Deaths of uncertain cause will be recorded separately and included in sensitivity analyses. |
From enrollment up to 20 years.
|
|
Cumulative incidence of a first major polyp-related complication
Tidsramme: From enrollment up to 20 years.
|
Time from enrollment to the first episode of intussusception, bowel obstruction, or gastrointestinal bleeding that results in hospitalization, emergency surgery or endoscopic treatment, or transfusion. Preventive polypectomy without an acute complication is excluded. Repeat episodes and the individual components will also be documented and summarized separately. |
From enrollment up to 20 years.
|
|
Age at clinical diagnosis of PJS
Tidsramme: At enrollment, using available historical records.
|
Age, in years, when the participant first met documented clinical diagnostic criteria for PJS. The evidence source and precision of the date will be recorded. Median, interquartile range, and the number with available information will be reported; molecularly ascertained participants without a clinical diagnosis will be identified separately. |
At enrollment, using available historical records.
|
|
Baseline gastrointestinal polyp involvement by anatomical site
Tidsramme: At enrollment, using available historical and baseline records.
|
Number and proportion of participants with documented PJS-related polyps in each gastrointestinal site before or at baseline, with sites reported separately. Each proportion will use the number with sufficient information for that site as its denominator; unassessed or unknown sites will not be coded as negative. |
At enrollment, using available historical and baseline records.
|
|
Distribution of documented STK11 germline variant classifications and variant types
Tidsramme: At enrollment; updated classifications retained separately during follow-up.
|
Counts and proportions of participants and independent families by STK11 germline variant classification and predefined variant type. Testing method, scope, and interpretation date will be documented. Pathogenic/likely pathogenic findings, variants of uncertain significance, adequately assessed negative findings, limited testing, and no testing will be reported separately. Genotype-phenotype association analyses use the clinical endpoints defined elsewhere and are exploratory. |
At enrollment; updated classifications retained separately during follow-up.
|
Samarbejdspartnere og efterforskere
Publikationer og nyttige links
Generelle publikationer
- Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.
- Wagner A, Aretz S, Auranen A, Bruno MJ, Cavestro GM, Crosbie EJ, Goverde A, Jelsig AM, Latchford A, Leerdam MEV, Lepisto A, Puzzono M, Winship I, Zuber V, Moslein G. The Management of Peutz-Jeghers Syndrome: European Hereditary Tumour Group (EHTG) Guideline. J Clin Med. 2021 Jan 27;10(3):473. doi: 10.3390/jcm10030473.
- Gu GL, Zhang Z, Zhang YH, Yu PF, Dong ZW, Yang HR, Yuan Y. Detection and analysis of common pathogenic germline mutations in Peutz-Jeghers syndrome. World J Gastroenterol. 2021 Oct 21;27(39):6631-6646. doi: 10.3748/wjg.v27.i39.6631.
- Jelsig AM, Wullum L, Kuhlmann TP, Ousager LB, Burisch J, Karstensen JG. Risk of Cancer and Mortality in Peutz-Jeghers Syndrome and Juvenile Polyposis Syndrome-A Nationwide Cohort Study With Matched Controls. Gastroenterology. 2023 Dec;165(6):1565-1567.e2. doi: 10.1053/j.gastro.2023.08.040. Epub 2023 Sep 1. No abstract available.
- de Leng WW, Jansen M, Carvalho R, Polak M, Musler AR, Milne AN, Keller JJ, Menko FH, de Rooij FW, Iacobuzio-Donahue CA, Giardiello FM, Weterman MA, Offerhaus GJ. Genetic defects underlying Peutz-Jeghers syndrome (PJS) and exclusion of the polarity-associated MARK/Par1 gene family as potential PJS candidates. Clin Genet. 2007 Dec;72(6):568-73. doi: 10.1111/j.1399-0004.2007.00907.x. Epub 2007 Oct 9.
- Neyaz A, Husain N, Deodhar M, Khurana R, Shukla S, Arora A. Synchronous Cervical Minimal Deviation Adenocarcinoma, Gastric Type Adenocarcinoma and Lobular Endocervical Glandular Hyperplasia Along with STIL in Peutz-Jeghers Syndrome: Eliciting Oncogenesis Pathways. Turk Patoloji Derg. 2019;35(3):247-253. doi: 10.5146/tjpath.2017.01406.
- van Lier MG, Westerman AM, Wagner A, Looman CW, Wilson JH, de Rooij FW, Lemmens VE, Kuipers EJ, Mathus-Vliegen EM, van Leerdam ME. High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome. Gut. 2011 Feb;60(2):141-7. doi: 10.1136/gut.2010.223750.
- Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH, Luk GD. Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med. 1987 Jun 11;316(24):1511-4. doi: 10.1056/NEJM198706113162404.
- Banno K, Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, Hirasawa A, Aoki D. Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review). Oncol Lett. 2013 Nov;6(5):1184-1188. doi: 10.3892/ol.2013.1527. Epub 2013 Aug 16.
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Neoplasmer
- Genetiske sygdomme, medfødte
- Tarmsygdomme
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Hudsygdomme
- Pigmenteringsforstyrrelser
- Neoplastiske syndromer, arvelig
- Intestinal polypose
- Hyperpigmentering
- Lentigo
- Melanose
- Medfødte, arvelige og neonatale sygdomme og abnormiteter
- Hud- og bindevævssygdomme
- Peutz-Jeghers syndrom
Andre undersøgelses-id-numre
- HEIR-PJS-2026
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