Genetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT00033137

Collaborator

(none)

950

Enrollment

Location

Study Details

Study Description

Brief Summary

This study will investigate the genetic cause of Birt Hogg-Dube (BHD) syndrome and the relationship of this disorder to kidney cancer. BHD is a rare inherited condition characterized by papules, or bumps benign tumors involving hair follicles on the head and neck. People with BHD are at increased risk of developing kidney cancer. Scientists have identified the chromosome (strand of genetic material in the cell nucleus) that contains the BHD gene and the region of the gene on the chromosome. This study will try to learn more about:

The characteristics and type of kidney tumors associated with BHD
The risk of kidney cancer in people with BHD
Whether more than one gene causes BHD
The genetic mutations (changes) responsible for BHD

Patients with known or suspected Birt Hogg-Dube syndrome, and their family members, may be eligible for this study. Candidates will be screened with a family history and review of medical records, including pathology reports for tumors, and films of computed tomography (CT) and magnetic resonance imaging (MRI) scans.

Participants may undergo various tests and procedures, including the following:

Physical examination
Review of personal and family history with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor
Chest and other x-rays
Ultrasound (imaging study using sound waves)
MRI (imaging study using radiowaves and a magnetic field)
CT scans of the chest and abdomen (imaging studies using radiation)
Blood tests for blood chemistries and genetic testing
Skin evaluation, including a skin biopsy (surgical removal of a small skin tissue sample for microscopic evaluation)
Cheek swab or mouthwash to collect cells for genetic analysis
Lung function studies
Medical photography of skin lesions

These tests will be done on an outpatient basis in either one day or over 3 to 4 days. When the studies are complete, participants will receive counseling about the findings and recommendations. Patients with kidney lesions may be asked to return periodically, such as every 3 to 36 months, based on their individual condition, to document the rate of progression of the lesions.

Condition or Disease	Intervention/Treatment	Phase
Kidney Neoplasms Kidney Cancer Pneumothorax FLCN Protien, Human

Detailed Description

Background:

BHD is a rare, autosomal dominantly inherited disorder which confers susceptibility to develop multifocal, bilateral renal cancer, spontaneous pneumothorax and fibrofolliculomas.
BHD is caused by mutations in the FLCN gene located on Chromosome17
Defining the genetic and biochemical pathways leading to renal tumorigenesis in BHD may lead to the development of new molecularly targeted drugs.

Objectives:

To define the types and characteristics (including patterns of growth) of renal cancer associated with BHD
To determine the risk of renal cancer, lung cysts and fibrofolliculomas in patients with BHD
To define the natural history of BHD related renal tumors
To determine if other genes contribute to BHD
Identify genotype / phenotype correlations

Eligibility:

Patients suspected or known to have phenotype or genotype suggestive of Birt Hogg Dube, such as:
Patients with histologically confirmed fibrofolliculomas,
Patients with clinical evidence of multiple skin papules consistent with fibrofolliculomas, and/or a family history of spontaneous pneumothorax or kidney cancer
Patients with a known germline FLCN mutation
A relative (related by blood) of an individual with a confirmed or suspected diagnosis of BHD

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 the BHD gene and to assess the relative activity of various germline and somatic mutations.
We will determine if there is a relationship between mutation and disease manifestations and phenotype.

Study Design

Study Type:

Observational

Anticipated Enrollment :

950 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Birt Hogg Dube' Syndrome: Identification of the Disease Gene, and Characterization of the Predisposition to Renal Cancer

Actual Study Start Date :

May 13, 2002

Arms and Interventions

Arm	Intervention/Treatment
Family Members A relative of a patient with a confirmed or suspected diagnosis of BHD (related by blood)
Non-Biologic Family Members Spouses enrolled primarily for linkage analysis(Spouses have been removed from the inclusion criteria for this study. This closed cohort has been created for spouses previously enrolled on study.)
Patients Patients with phenotype or genotype suggestive of Birt Hogg Dub(SqrRoot)(Copyright) and/or Renal tumor histology consistent with BHD

Outcome Measures

Primary Outcome Measures

Identify genotype / phenotype correlations. [on-going]
Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Determine risk of renal cancer, lung cysts and fibrofollicullomas in patients with BHD. [on-going]
Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Determine if other genes contribute to BHD. [on-going]
Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Define types and characteristics (including patterns of growth) of renal cancer associated with BHD. [on-going]
Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer
Define the natural history of BHD related renal tumors. [on-going]
Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

-INCLUSION CRITERIA:

Patients suspected or known to have phenotype or genotype suggestive of Birt Hogg

Dube, such as:

Patients with at least one histologically confirmed fibrofolliculomas, or
Patients with clinical evidence of multiple skin papules (without fibrofolliculoma biopsy confirmation) and a personal or family history of spontaneous pneumothorax / or kidney cancer, or
Patients with spontaneous pneumothorax and skin papules or kidney cancer and a positive family history of spontaneous pneumothorax, skin papules or kidney cancer, or
Patients with a known germline FLCN gene mutation

Renal tumor histology consistent with BHD, including, but not limited to those suggestive of chromophobe, oncocytic neoplasm or oncocytoma.
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.

Participants must be greater than or equal to 2 years of age.
A relative (related by blood) of a patient with a confirmed or suspected diagnosis of BHD.