Study of 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.