Frequency, Clinical Phenotype and Genetic Analysis of Heritable Kidney Cancer Syndromes

This study will investigate the frequency, clinical phenotype, management and molecular genetic defects of heritable kidney cancer syndromes. Families with kidney cancer with known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a germline kidney cancer will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed in situations in which the genetic basis of the disorder has not been elucidated. This research will have a significant impact on the overall management of heritable kidney cancer syndromes patients and family members who are at risk for heritable kidney cancer syndromes. The study will ultimately facilitate the development of novel screening, prevention and treatment strategies for these individuals with the syndrome. In addition this study could have impact on the management of patients with personal and/or family history of heritable kidney cancer syndromes.

Study Overview

• Status: Recruiting
• Conditions: Kidney Cancer; Renal Cell Carcinoma; ALK Gene Mutation; MET Gene Mutation; HLRCC; Renal Tumor Histology; Cutaneous Leiomyoma; BAP1 Tumor Predisposition Syndrome; VHL Syndrome; Birt-Hogg-Dube Syndrome; Familial Renal Cancer; FLCN Gene Mutation; FH Gene Mutation; Cutaneous Leiomyomata With Uterine Leiomyomata
• Intervention / Treatment: Genetic: Gene test

Detailed Description

Background:

• The genetic etiology of heritable kidney cancer syndromes remains to be determined.

Objectives:

• Define the risk of developing renal cance in heritable kidney cancer syndromes
• Define the types and characteristics (including patterns of growth) of heritable kidney cancer syndromes.
• Determine genotype/phenotype correlations.
• To characterize the natural and clinical histories of heritable kidney cancer syndromes.
• To determine the genetic etiology of heritable kidney cancer syndromes.

Design:

• These rare families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors.
• Genetic testing will be offered to gain appreciation of the effect of mutations on the relative activity of various germline and somatic mutations.
• To determine if there is a relationship between mutation and disease manifestations and phenotype.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Yunze Xu, Ph.D.; Phone Number: +8618801967501; Email: rjxuyunze@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Ethics Committee of Shanghai Renji Hospital
      • Contact: Qi Lu; Phone Number: +86021-68383364; Email: rjllb3364@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with known or suspected heritable kidney cancer syndromes and their biologic family members with heritable kidney cancer syndromes will be recruited primarily from the urology, oncology, and genetics communities worldwide.

Description

Inclusion Criteria:

• Participants must be greater than or equal to 2 years of age. All patients and guardians (for children younger than 18 years of age) must sign an informed consent document indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed. Patients under the age of 18 but who are age 13 or older will be asked to sign an assent document prior to participation.
• Individuals and biologic family members with a suspected or an established diagnosis of a heritable kidney cancer syndrome in which the disease gene is known, including von Hippel-Lindau (VHL) and hereditary papillary renal carcinoma (HPRC).
• Individuals and biologic family members with a suspected or an established diagnosis of a heritable kidney cancer syndrome in which the disease gene is not yet known, specifically hereditary forms of Type II papillary renal cancer, clear cell renal carcinoma, renal oncocytoma, chromophobe renal carcinoma or Birt Hogg Dube.
• Individuals and biologic family members who have heritable kidney cancer syndromes of suspected, but not proven genetic etiology, including families with more than one individual affected by the same or related cancers.
• Subject Enrollment Categories (to include both affected and unaffected biologic relatives).

Exclusion Criteria:

• Pregnant women are excluded from enrollment onto this study because there is no direct benefit for participating in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient with heritable kidney cancer syndrome; Patients with known or suspected heritable kidney cancer syndromes, including VHL and HLRCC Disease.	Genetic: Gene test; Next generation sequencing of blood, urine and/or benign and malignant tissue of patients and family members with known or suspected heritable kidney cancer syndromes, including VHL and HLRCC Disease.
Family members of heritable kidney cancer syndrome; Family members (related by blood) of patients who have or are suspected of having heritable kidney cancer syndromes, including VHL and HLRCC Disease.	Genetic: Gene test; Next generation sequencing of blood, urine and/or benign and malignant tissue of patients and family members with known or suspected heritable kidney cancer syndromes, including VHL and HLRCC Disease.
Not proven genetic etiology; Patients and biologic family members with a heritable kidney cancer syndrome of suspected, but not proven genetic etiology.	Genetic: Gene test; Next generation sequencing of blood, urine and/or benign and malignant tissue of patients and family members with known or suspected heritable kidney cancer syndromes, including VHL and HLRCC Disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical phenotypes of patients of heritable kidney cancer syndromes	Chart review of disease outcome	5 years
Genotypes of patients of heritable kidney cancer syndromes	Genotyping for genetic variants that could modify the risk of cancer in subjects.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical phenotypes of family members of the patients	Questionnaire and chart review of the clinical phenotype	5 years
Prevalence of germline variants in the unselected general population of renal cancer patients	Frequency of germline pathogenic/likely pathogenic variants in renal cancer	5 years

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Peking University First Hospital; Shanghai Zhongshan Hospital; First Affiliated Hospital, Sun Yat-Sen University; Huashan Hospital; Tongji Hospital; Second Affiliated Hospital, School of Medicine, Zhejiang University; Shanghai 10th People's Hospital; Ruijin Hospital; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Zhejiang Provincial People's Hospital
• Investigators: Study Chair: Jin Zhang, Renji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: July 4, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Neoplastic Syndromes, Hereditary; Neoplasms, Connective Tissue; Abnormalities, Multiple; Neoplasms, Muscle Tissue; Neurocutaneous Syndromes; Ciliopathies; Angiomatosis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Neoplasms; Carcinoma, Renal Cell; Syndrome; Leiomyoma; Myofibroma; Von Hippel-Lindau Disease; Birt-Hogg-Dube Syndrome
• Other Study ID Numbers: RENJI-IKCS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No