RATIONALE: Studying individuals and families at high risk for melanoma may help to identify other persons at risk and the genes involved in the development of melanoma.

PURPOSE: Study to identify genetic and environmental factors related to melanoma risk in individuals and families at high risk for melanoma.

OBJECTIVES:

• Evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing individuals and families to melanoma.
• Evaluate potential precursor states of disease in families at risk for melanoma.
• Quantify risks of melanoma, pancreatic cancer, and other cancers in family members.
• Map, clone, and determine function of tumor susceptibility genes in melanoma-prone families, including modifier genes such as pigmentation or dysplastic nevi genes.
• Identify genetic determinants and gene-environmental interactions conferring melanoma (and other cancer) risk in individuals and families.
• Evaluate gene-gene and gene-environmental interactions in melanoma (and other cancer) formation in individuals and families.
• Educate and counsel study participants about their melanoma risk and methods for primary and secondary prevention of melanoma.

OUTLINE: One family member completes a family history questionnaire for verification of diagnosis and construction of a family pedigree. Information collected from all individuals may include skin examination and sun exposure history, overview and close-up photographs, medical history, and limited physical examination (entire skin exam for all family members and lymph node palpation for individuals with current or prior melanoma). Some individuals may also undergo an MRI and/or a skin biopsy.

Blood is collected for localizing genetic loci, identifying genes, and evaluating phenotype/genotype correlations. Each family is tested for mutations in CDKN2A and CDK4 and other potential melanoma susceptibility genes.

Each family member receives educational materials about sun protective behavior, skin self-examination, recognition of melanoma warning signs, recognition of dysplastic nevi, and changes worrisome for melanoma. Each person also receives individual risk counseling about melanoma based on personal cutaneous phenotype and position in the pedigree.

Individuals are followed every few years to document changes in their skin exam as sun exposure is decreased and to collect information from those who have undergone mole biopsies . Specific nevi are followed and photographed.

When the genetic testing results would impact clinical care recommendations, genetic testing and notification of results are offered only to participants who, after appropriate education and counseling, want to know their individual genetic status. Because of the exploratory nature of this study, results are not routinely returned to participants at this time.

A certificate of confidentiality protecting the identity of research participants in this project has been issued by the National Cancer Institute.

PROJECTED ACCRUAL: A total of 100 additional families will be accrued for this study within the next few years.

• Genetic: microarray analysis
• Genetic: mutation analysis
• Other: cytology specimen collection procedure
• Other: educational intervention
• Other: physiologic testing
• Procedure: evaluation of cancer risk factors
• Procedure: study of high risk factors

• Goldstein AM, Chan M, Harland M, Hayward NK, Demenais F, Timothy Bishop D, Azizi E, Bergman W, Bianchi-Scarra G, Bruno W, Calista D, Cannon Albright LA, Chaudru V, Chompret A, Cuellar F, Elder DE, Ghiorzo P, Gillanders EM, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Teresa Landi M, Lang J, Leachman SA, Mackie RM, Magnusson V, Mann GJ, Newton Bishop J, Palmer JM, Puig S, Puig-Butille JA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E. Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet. 2007 Feb;44(2):99-106. Epub 2006 Aug 11.
• Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, Azizi E, Bianchi-Scarra G, Bishop DT, Bressac-de Paillerets B, Bruno W, Calista D, Cannon Albright LA, Demenais F, Elder DE, Ghiorzo P, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, Mackie RM, Magnusson V, Mann GJ, Niendorf K, Newton Bishop J, Palmer JM, Puig S, Puig-Butille JA, de Snoo FA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E; Melanoma Genetics Consortium (GenoMEL). High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 2006 Oct 15;66(20):9818-28.
• Laud K, Marian C, Avril MF, Barrois M, Chompret A, Goldstein AM, Tucker MA, Clark PA, Peters G, Chaudru V, Demenais F, Spatz A, Smith MW, Lenoir GM, Bressac-de Paillerets B; French Hereditary Melanoma Study Group. Comprehensive analysis of CDKN2A (p16INK4A/p14ARF) and CDKN2B genes in 53 melanoma index cases considered to be at heightened risk of melanoma. J Med Genet. 2006 Jan;43(1):39-47. Epub 2005 Jun 3.
• Goldstein AM, Landi MT, Tsang S, Fraser MC, Munroe DJ, Tucker MA. Association of MC1R variants and risk of melanoma in melanoma-prone families with CDKN2A mutations. Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2208-12.
• Harland M, Taylor CF, Chambers PA, Kukalizch K, Randerson-Moor JA, Gruis NA, de Snoo FA, ter Huurne JA, Goldstein AM, Tucker MA, Bishop DT, Bishop JA. A mutation hotspot at the p14ARF splice site. Oncogene. 2005 Jun 30;24(28):4604-8.
• Goldstein AM, Struewing JP, Fraser MC, Smith MW, Tucker MA. Prospective risk of cancer in CDKN2A germline mutation carriers. J Med Genet. 2004 Jun;41(6):421-4.
• Gillanders E, Juo SH, Holland EA, Jones M, Nancarrow D, Freas-Lutz D, Sood R, Park N, Faruque M, Markey C, Kefford RF, Palmer J, Bergman W, Bishop DT, Tucker MA, Bressac-de Paillerets B, Hansson J, Stark M, Gruis N, Bishop JN, Goldstein AM, Bailey-Wilson JE, Mann GJ, Hayward N, Trent J; Lund Melanoma Study Group; Melanoma Genetics Consortium. Localization of a novel melanoma susceptibility locus to 1p22. Am J Hum Genet. 2003 Aug;73(2):301-13. Epub 2003 Jul 3.
• Rutter JL, Goldstein AM, Davila MR, Tucker MA, Struewing JP. CDKN2A point mutations D153spl(c.457G>T) and IVS2+1G>T result in aberrant splice products affecting both p16INK4a and p14ARF. Oncogene. 2003 Jul 10;22(28):4444-8.
• Bishop DT, Demenais F, Goldstein AM, Bergman W, Bishop JN, Bressac-de Paillerets B, Chompret A, Ghiorzo P, Gruis N, Hansson J, Harland M, Hayward N, Holland EA, Mann GJ, Mantelli M, Nancarrow D, Platz A, Tucker MA; Melanoma Genetics Consortium. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002 Jun 19;94(12):894-903.
• Feng Y, Shi J, Goldstein AM, Tucker MA, Nelson MA. Analysis of mutations and identification of several polymorphisms in the putative promoter region of the P34CDC2-related CDC2L1 gene located at 1P36 in melanoma cell lines and melanoma families. Int J Cancer. 2002 Jun 20;99(6):834-8. Erratum in: Int J Cancer 2002 Aug 20;100(6):733-4.
• Goldstein AM, Chidambaram A, Halpern A, Holly EA, Guerry IV D, Sagebiel R, Elder DE, Tucker MA. Rarity of CDK4 germline mutations in familial melanoma. Melanoma Res. 2002 Feb;12(1):51-5.
• Buckel TB, Goldstein AM, Fraser MC, Rogers B, Tucker MA. Recent tanning bed use: a risk factor for melanoma. Arch Dermatol. 2006 Apr;142(4):485-8.
• Goldstein AM, Tucker MA. A piece of the melanoma puzzle. J Natl Cancer Inst. 2005 Oct 19;97(20):1486-7. No abstract available.
• Goldstein AM. Familial melanoma, pancreatic cancer and germline CDKN2A mutations. Hum Mutat. 2004 Jun;23(6):630.
• Millen AE, Tucker MA, Hartge P, Halpern A, Elder DE, Guerry D 4th, Holly EA, Sagebiel RW, Potischman N. Diet and melanoma in a case-control study. Cancer Epidemiol Biomarkers Prev. 2004 Jun;13(6):1042-51.
• Rutter JL, Bromley CM, Goldstein AM, Elder DE, Holly EA, Guerry D 4th, Hartge P, Struewing JP, Hogg D, Halpern A, Sagebiel RW, Tucker MA. Heterogeneity of risk for melanoma and pancreatic and digestive malignancies: a melanoma case-control study. Cancer. 2004 Dec 15;101(12):2809-16.
• Kefford R, Bishop JN, Tucker M, Bressac-de Paillerets B, Bianchi-Scarra G, Bergman W, Goldstein A, Puig S, Mackie R, Elder D, Hansson J, Hayward N, Hogg D, Olsson H; Melanoma Genetics Consortium. Genetic testing for melanoma. Lancet Oncol. 2002 Nov;3(11):653-4. No abstract available.
• Tucker MA, Fraser MC, Goldstein AM, Struewing JP, King MA, Crawford JT, Chiazze EA, Zametkin DP, Fontaine LS, Clark WH Jr. A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families. Cancer. 2002 Jun 15;94(12):3192-209.

DISEASE CHARACTERISTICS:

• Either of the following:

  • Individuals with a personal or family history of melanoma of an unusual type, pattern, or number

  • Individuals with known or suspected factor(s) predisposing to melanoma (e.g., dysplastic nevi)

    • Genetic (e.g., albinism) or congenital factors (e.g., large congenital nevi)
    • Unusual demographic features (very young age of onset, multiple melanomas, prior history of heritable retinoblastoma, Hodgkin's disease, lymphoma, or organ transplantation)
• At least 3 living affected cases with invasive melanoma must be available for study of familial melanoma
• Diagnoses must be verifiable

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified