Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma

Study Description:

Melanoma-prone families and individuals with risk factors for melanoma, including people with Spitzoid tumors and giant congenital nevi, are human models of susceptibility to neoplasia from which mechanisms of cancer susceptibility may be elucidated. For most of the high-risk cancer susceptibility genes, including CDKN2A and CDK4 in melanoma-prone families, germline mutations conferring risk have been found through family studies. Investigations of individuals and families at high risk of melanoma have led to etiologic clues that are important in the general population and have identified persons most likely to benefit from chemoprevention trials and screening programs aimed at early diagnosis of melanoma.

Objectives:

• To evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to melanoma
• To evaluate potential precursor states of disease in individuals and families at risk
• To quantify risks of melanoma, pancreatic cancer, and other cancers in family members and individuals with an elevated risk for melanoma
• To map, clone, and determine function of tumor susceptibility genes in melanoma-prone families, including modifier genes such as pigmentation or dysplastic nevi genes
• To identify genetic determinants and gene-environmental interactions conferring melanoma (and other cancer) risk in individuals and families
• To evaluate gene-gene and gene-environment interactions in melanoma (and other cancer) formation
• To characterize genetic alternations in precursor lesions and melanomas that occur in individuals and families with an increased risk of melanoma.
• To educate and counsel study participants about their melanoma risk and methods for primary and secondary prevention of melanoma
• To develop educational materials for medical professionals and high-risk family members

Endpoints:

Primary endpoints:

All cancers that occur in individuals and families at high risk of melanoma

Secondary endpoints:

Secondary endpoints are markers of pre-malignant conditions, such as dysplastic nevi, giant congenital nevi, and Spitzoid tumors

• INCLUSION CRITERIA:
• On referral, persons >=4 weeks old of any sex, race or ethnicity will be considered for inclusion in the study because of the criteria noted below.
• Affected: An individual who meets any of the following criteria will be eligible to participate in this study:

• personal medical history of melanoma of an unusual type, pattern, or number diagnosed at any age; or,
• known or suspected factor(s) predisposing to melanoma, either genetic or congenital factors (giant congenital nevi, dysplastic nevi, Spitzoid tumors), or unusual demographic features (e.g., very young age of onset, multiple melanomas, previous history of heritable retinoblastoma, Hodgkin s disease, lymphoma, immunodeficiency syndrome, or organ transplant).
• Ability of the individual or their parent or legal guardian, to understand, and their willingness to provide informed consent.
• Unaffected: An individual who meets any of the following criteria will be eligible to participate in this study:

• family medical history of melanoma of an unusual type, pattern, or number; or,
• known or suspected factor(s) predisposing to melanoma, either genetic or congenital factors (giant congenital nevi, dysplastic nevi. Spitzoid tumors), or unusual demographic features (e.g., very young age of onset, multiple melanomas, previous history of heritable retinoblastoma, Hodgkin s disease, lymphoma, immunodeficiency syndrome, or organ transplant).
• Ability of the individual or their parent, or legal guardian to understand, and their willingness to provide informed consent.
• Personal and family medical history must be verified through questionnaires, interviews, and review of pathology slides and medical records.

Exclusion criteria

• Referred individuals and families for whom reported diagnoses cannot be verified;
• Inability to provide informed consent