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

NCT ID: NCT00050752

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

1130 participants

Study Classification

OBSERVATIONAL

Study Start Date

2003-02-24

Brief Summary

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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.

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Detailed Description

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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 cause HLRCC

Eligibility:

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

* 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
* A relative (related by blood) of an individual with a confirmed or suspected diagnosis of HLRCC

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.

Conditions

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Renal Tumor Histology Cutaneous Leiomyoma Kidney Cancer

Keywords

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Renal Cancer Hereditary Leiomyomatosis Uterine Fibroid Cutaneous Leiomyoma Natural History

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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1 / Individuals

Individuals with known or suspected Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)

No interventions assigned to this group

2 / Family Members

Family members (related by blood) of individuals who have or are suspected of having Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC)

No interventions assigned to this group

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.)

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Individuals 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; or
* Cutaneous leiomyoma and uterine leiomyoma; or
* Multiple cutaneous leiomyoma; or
* Kidney cancer and uterine leiomyomata; or
* Renal tumor histology consistent with HLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II
* All participants 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.
* Participants must be \>= 2 years of age.
* A relative (related by blood) of an individual with a confirmed or suspected diagnosis of HLRCC.

Exclusion Criteria

None
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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W. Marston Linehan, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Deborah A Nielsen, R.N.

Role: CONTACT

Phone: (240) 760-6247

Email: [email protected]

W. Marston Linehan, M.D.

Role: CONTACT

Phone: (240) 858-3700

Email: [email protected]

Facility Contacts

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For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Role: primary

References

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Zbar B, Tory K, Merino M, Schmidt L, Glenn G, Choyke P, Walther MM, Lerman M, Linehan WM. Hereditary papillary renal cell carcinoma. J Urol. 1994 Mar;151(3):561-6. doi: 10.1016/s0022-5347(17)35015-2.

Reference Type BACKGROUND
PMID: 8308957 (View on PubMed)

Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574.

Reference Type BACKGROUND
PMID: 8493574 (View on PubMed)

Linehan WM, Lerman MI, Zbar B. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA. 1995 Feb 15;273(7):564-70. No abstract available.

Reference Type BACKGROUND
PMID: 7837390 (View on PubMed)

Related Links

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Other Identifiers

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03-C-0066

Identifier Type: -

Identifier Source: secondary_id

030066

Identifier Type: -

Identifier Source: org_study_id

NCT00055627

Identifier Type: -

Identifier Source: nct_alias