RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer and may help doctors identify patients who are at risk for cancer.

PURPOSE: This clinical trial is studying cancer risk and gene identification in patients and families with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC).

OBJECTIVES:

• Determine the types and characteristics (e.g., patterns of growth) of renal cancer in patients and families with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.
• Determine the risk of renal cancer in patients and their families with HLRCC.
• Determine the incidence of germline fumarate hydratase (fumerase) mutations in this population.
• Determine whether other genes are responsible for HLRCC.
• Correlate genotype and phenotype in this population.
• Determine the clinical manifestations of HLRCC.

OUTLINE: Detailed family and medical histories are obtained from participants. Participants then undergo one or more of the following: physical examination, blood draw, imaging studies, and karyotypic analysis.

Blood or buccal smears are examined by linkage or DNA analysis and other genetic studies.

Participants may receive an explanation of study findings, appropriate counseling about their own status, and recommendations for follow-up/treatment. Participants may receive DNA results from analysis of their fumarate hydratase gene.

Some participants with indeterminate renal lesions are followed every 3-36 months, depending on the characteristics (e.g., size and/or growth) of the lesion.

PROJECTED ACCRUAL: A total of 90-120 participants will be accrued for this study within 3 years.

• Genetic: DNA ploidy analysis
• Genetic: cytogenetic analysis
• Genetic: genetic linkage analysis
• Genetic: microarray analysis
• Genetic: mutation analysis
• Other: medical chart review

• Wei MH, Toure O, Glenn GM, Pithukpakorn M, Neckers L, Stolle C, Choyke P, Grubb R, Middelton L, Turner ML, Walther MM, Merino MJ, Zbar B, Linehan WM, Toro JR. Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer. J Med Genet. 2006 Jan;43(1):18-27. Epub 2005 Jun 3.
• Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL, Merino M, Trepel J, Zbar B, Toro J, Ratcliffe PJ, Linehan WM, Neckers L. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell. 2005 Aug;8(2):143-53.
• Matyakhina L, Freedman RJ, Bourdeau I, Wei MH, Stergiopoulos SG, Chidakel A, Walther M, Abu-Asab M, Tsokos M, Keil M, Toro J, Linehan WM, Stratakis CA. Hereditary leiomyomatosis associated with bilateral, massive, macronodular adrenocortical disease and atypical cushing syndrome: a clinical and molecular genetic investigation. J Clin Endocrinol Metab. 2005 Jun;90(6):3773-9. Epub 2005 Mar 1.
• Linehan WM, Zbar B. Focus on kidney cancer. Cancer Cell. 2004 Sep;6(3):223-8. Review. No abstract available. Erratum in: Cancer Cell. 2004 Oct;6(4):423.
• Choyke PL, Glenn GM, Walther MM, Zbar B, Linehan WM. Hereditary renal cancers. Radiology. 2003 Jan;226(1):33-46. Review.
• Hwang JJ, Uchio EM, Linehan WM, Walther MM. Hereditary kidney cancer. Urol Clin North Am. 2003 Nov;30(4):831-42. Review.
• Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol. 2003 Dec;170(6 Pt 1):2163-72. Review.
• Toro JR, Nickerson ML, Wei MH, Warren MB, Glenn GM, Turner ML, Stewart L, Duray P, Tourre O, Sharma N, Choyke P, Stratton P, Merino M, Walther MM, Linehan WM, Schmidt LS, Zbar B. Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America. Am J Hum Genet. 2003 Jul;73(1):95-106. Epub 2003 May 22.
• Zbar B, Klausner R, Linehan WM. Studying cancer families to identify kidney cancer genes. Annu Rev Med. 2003;54:217-33. Epub 2001 Dec 3. Review.

DISEASE CHARACTERISTICS:

• Patients with known or suspected hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome and their family members

  • Spouses also eligible

• One or more family members must have 1 of the following:

  • 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 type II papillary carcinoma

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Negative pregnancy test (if undergoing imaging tests)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Concurrent standard-care radiotherapy allowed

Surgery

• Concurrent standard-care surgery allowed