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Hereditary Leiomyomatosis Renal Cell Cancer - Study of the Genetic Cause and the Predisposition to Renal Cancer

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ClinicalTrials.gov Identifier: NCT00050752
Recruitment Status : Recruiting
First Posted : December 18, 2002
Last Update Posted : January 19, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Study Description
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Brief Summary:

This study will investigate what causes hereditary leiomyomatosis renal (kidney) cell cancer, or HLRCC, and how the disease is related to the development of kidney tumors. Leiomyomas are benign (non-cancerous) tumors arising from smooth muscle. HLRCC can cause various health problems. Some people develop red bumps on their skin that can be painful at times. Some women with HLRCC can develop leiomyomas of the uterus. In some families, people with HLRCC develop kidney tumors. This study will try to determine:

  • What gene changes (mutations) cause HLRCC
  • What kind of kidney tumors develop in HLRCC and how they grow
  • What the chance is that a person with HLRCC will develop a kidney tumor

People with known or suspected HLRCC (and their family members of any age) may be eligible for this study. This includes people in families in which one or more members has skin leiomyoma and kidney cancer; skin leiomyoma and uterine leiomyoma; multiple skin leiomyomas; kidney cancer and uterine leiomyomas, or kidney cancer consistent with HLRCC, including, but not limited to, collecting duct or papillary, type II. Candidates will be screened with a physical examination, family history, and, for affected family members, a review of medical records, including pathology slides and computed tomography (CT) or magnetic resonance imaging (MRI) scans.

Participants will undergo tests and procedures that may include the following:

  • Review of medical records, x-rays, and tissue slides
  • Physical examination and family history
  • Skin examination
  • Gynecological examination for women
  • Interviews with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor

  • Blood tests for:

    1. Genetic research to identify the gene responsible for HLRCC
    2. Evaluation of liver, kidney, heart, pancreas, and thyroid function
    3. Complete blood count and clotting profile
    4. Pregnancy test for pre-menopausal women
    5. PSA test for prostate cancer in men over age 40
  • CT or MRI scans (for participants 15 years of age and older only)
  • Skin biopsy (surgical removal of a small sample of skin tissue)
  • Cheek swab or mouth rinse to collect cells for genetic analysis
  • Medical photographs of lesions
  • Questionnaire

When the tests are completed, participants will discuss the results with a doctor and possibly a genetic nurse or genetic counselor. The genetic findings will not be revealed to participants because their meaning and implications may not yet be understood. Participants may be asked to return to NIH from every 3 months to every 3 years, depending on their condition, for follow-up examinations and tests.


Condition or disease
Renal Tumor Histology Cutaneous Leiomyoma Kidney Cancer

Detailed Description:

Background:

  • Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a rare autosomal dominantly inherited disorder which confers susceptibility to develop cutaneous and uterine leiomyomas and renal cell carcinoma.
  • HLRCC is caused by mutations in the Krebs cycle enzyme, fumarate hydratase localized on chromosome 1q42.3-q43.

Objectives:

  • Define the risk of developing renal cancer, cutaneous leiomyoma and uterine leiomyoma in this hereditary cancer syndrome
  • Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC.
  • Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations.
  • Determine genotype/phenotype correlations.
  • Determine if other genes caused HLRCC.

Eligibility:

-An individual from a family in which one or more biological family members have:

  • Cutaneous leiomyoma and kidney cancer.
  • Cutaneous leiomyoma and uterine leiomyoma.
  • Multiple cutaneous leiomyoma.
  • Kidney cancer and uterine leiomyomata.
  • Renal tumor histology consistent with HLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II.

Design:

  • These rare biological 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.
  • We will determine if there is a relationship between mutation and disease phenotype.
Study Design
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Study Type : Observational
Estimated Enrollment : 950 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Hereditary Leiomyomatosis Renal Cell Cancer (HLRCC): Identification of the Disease Gene and Characterization of the Predisposition to Renal Cancer
Actual Study Start Date : February 24, 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Cancer

Groups and Cohorts
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Group/Cohort
1 / Patients
Patients with known or suspected Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)
2 / Family Members
Family members (related by blood) of patients who have or are suspected of having Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)
3 / Non-Biologic Family Members
Spouses enrolled primarily for linkage analysis (Spouses have been removed from the inclusion criteria for this study. This closed cohort is for spouses previously enrolled on study.)


Outcome Measures
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Primary Outcome Measures :
  1. Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations. [ Time Frame: on-going ]
    Molecular genetic differences between normal and tumorigenic fumarate hydratase (fumerase) mutations.

  2. Determine the clinical manifestations of HLRCC [ Time Frame: on-going ]
    Collection of blood, urine and/or benign and malignant tissue.

  3. Determine if other genes cause HLRCC. [ Time Frame: on-going ]
    Molecular genetic differences between normal and tumorigenic cells.

  4. Determine genotype/phenotype correlations. [ Time Frame: on-going ]
    Detection and expression analysis of gene(s).

  5. Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC. [ Time Frame: on-going ]
    Detection and expression analysis of gene(s).

  6. Define the risk of developing renal cancer, cutaneous leiomyoma and uterine leiomyoma in this hereditary cancer syndrome. [ Time Frame: on-going ]
    Collection of blood, urine and/or benign and malignant tissue.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
An individual (including patient) from a family in which one or more family member have: cutaneous leiomyoma and kidney cancer, cutaneous leiomyoma and uterine leiomyoma, multiple cutaneous leiomyoma, kidney cancer and uterine leiomyomata, renal tumor histology consistent with HLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II.
Criteria
  • INCLUSION CRITERIA:

Patients suspected or known to have phenotype or genotype suggestive of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC), such as:

  • Cutaneous leiomyoma and kidney cancer
  • Cutaneous leiomyoma and uterine leiomyoma
  • Multiple cutaneous leiomyoma
  • Kidney cancer and uterine leiomyomata
  • Renal tumor histology consistent with HRLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II
  • All patients and parents/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 (Bullet) 2 years of age.
  • A relative (related by blood) of a patient with a confirmed or suspected diagnosis of HLRCC.

EXCLUSION CRITERIA:

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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00050752


Contacts
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Contact: Deborah A Nielsen, R.N. (240) 760-6247 deborah.nielsen@nih.gov
Contact: W. Marston Linehan, M.D. (240) 858-3700 wl3e@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: W. Marston Linehan, M.D. National Cancer Institute (NCI)
More Information
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Additional Information:

Publications:

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00050752    
Obsolete Identifiers: NCT00055627
Other Study ID Numbers: 030066
03-C-0066
First Posted: December 18, 2002    Key Record Dates
Last Update Posted: January 19, 2022
Last Verified: October 8, 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Renal Cancer
Hereditary Leiomyomatosis
Uterine Fibroid
Cutaneous Leiomyoma
Natural History
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Kidney Neoplasms
Leiomyoma
Myofibroma
Leiomyomatosis
Disease Susceptibility
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
 Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Connective Tissue Diseases
Disease Attributes
Pathologic Processes