Clinical trial NCT00050752: Hereditary Leiomyomatosis Renal Cell Cancer - Study of the Genetic Cause and the Predisposition to Renal Cancer
Official title: Hereditary Leiomyomatosis Renal Cell Cancer (HLRCC): Identification of the Disease Gene, and Characterization of the Predisposition to Renal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Renal Tumor Histology
Cutaneous Leiomyoma
Kidney Cancer
Keywords: Renal Cancer
Hereditary Leiomyomatosis
Uterine Fibroid
Cutaneous Leiomyoma
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2002-12-18
Enrollment: 1130
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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 \>= 2 years of age.
* A relative (related by blood) of a patient with a confirmed or suspected diagnosis of HLRCC.

EXCLUSION CRITERIA:

None

Primary outcomes:
measure: Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations.
timeFrame: on-going
measure: Determine the clinical manifestations of HLRCC
timeFrame: on-going
measure: Determine if other genes cause HLRCC.
timeFrame: on-going
measure: Determine genotype/phenotype correlations.
timeFrame: on-going
measure: Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC.
timeFrame: on-going
measure: Define the risk of developing renal cancer, cutaneous leiomyoma and uterine leiomyoma in this hereditary cancer syndrome.
timeFrame: on-going
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: W. Marston Linehan, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.