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

NCT00040352 | Recruiting

• 2 other identifiers: 02021102-C-0211
• Study Type: observational
• Target: 3,000
• Locations: 1 country
• Sites: 2

Brief Summary

This study will investigate how genetic and environmental factors contribute to the development of melanoma, a type of skin cancer, and related conditions. Individuals \>=4 weeks with a personal or family history of melanoma or atypical spitzoid/Spitz tumor may be eligible for this study. Participants will:

• Fill out one or two questionnaires about their personal and family medical history.
• Provide written consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with melanomas, tumors, cancer, or other related illnesses for whom they are the next-of-kin or legally authorized representative.
• Donate a blood or cheek cell sample to be used for genetic studies. (The blood sample is collected through a needle in an arm vein. The cheek cell sample is obtained either by gently brushing the inside of the mouth with a soft brush or by swishing a tablespoon of mouthwash and then spitting it into a container.)
• Undergo a skin biopsy (removal of a small piece of skin tissue) for genetic study. For this procedure, the area of skin to be removed is numbed with a local anesthetic and a 1/4-inch piece of skin is excised with a cookie cutter-like instrument. The wound is then covered with a band-aid. Participants may be asked to travel to the NIH Clinical Center for evaluation, including a medical history, physical examination, and some of the following procedures:
• Full body skin examination to evaluate the type and number of moles and document any evidence of sun damage to the skin. The examination involves all the skin from the scalp to the bottoms of the feet. After the examination, a medical photographer will photograph the skin, with close-ups of skin lesions marked by the examiner. If there are parts of the skin the participant does not want examined or photographed, he or she can tell the examiner.
• Blood draw of about 120 milliliters (4 ounces) or less
• Skin biopsy
• Cheek cell sample
• X-rays, ultrasound and magnetic resonance imaging (MRI) studies to detect tumors or changes in tumors or other types of changes in specific tissues. MRI is a diagnostic test that uses strong magnetic fields and radiowaves to examine body tissues. The subject lies on a table that is moved into a large tunnel-like machine (the scanner) for about 45 minutes to 1 hour. When the tests are finished, a doctor will discuss the results with the participant and the need, if any, for clinical follow-up.

Conditions

Melanoma; Dysplastic Nevus Syndrome

Keywords

Skin Cancer; Risk Factors; Melanoma Precursors; Genetics; Melanoma

Outcome Measures

Primary Outcomes (1)

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

  1\. Identification of major susceptibility genes for melanoma and dysplastic nevi. 2. Prospective risk of melanoma after initial exam and melanoma education. 3. Mortality of melanoma in families. 4. Identification of other risk factors for familial melanoma. 5. Identification of other cancers in melanoma-prone individuals and families.

  Ongoing

Secondary Outcomes (1)

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

  Ongoing

Study Arms (2)

Affected Individual

An individual with personal medical history of melanoma of an unusual type, pattern, or number, a known or suspected condition predisposing to melanoma, either genetic or congenital factors (giant congenital nevi, dysplastic nevi, Spitzoid tumors), or unusual demographic features, or any of the other criteria noted in Section 4.1 of the protocol

Unaffected individual

A family member of an affected participant. Family members may include parents, siblings, children or extended family.

Eligibility Criteria

• Age: 4 Weeks - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All members of families with three or more living melanoma cases in the U.S. are eligible for inclusion in the study if the families are willing to participate.@@@@@@

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (6)

• Liang X, Pfeiffer RM, Li WQ, Brossard M, Burke LS, Wheeler W, Calista D, Fargnoli MC, Ghiorzo P, Peris K, Bianchi-Scarra G, Chaudru V, Zelenika D, Maeder D, Burdette L, Yeager M, Chanock S, Landi MT, Demenais F, Tucker MA, Goldstein AM, Yang XR. Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families. J Invest Dermatol. 2014 Feb;134(2):481-487. doi: 10.1038/jid.2013.316. Epub 2013 Jul 26.

  PMID: 23892592 BACKGROUND

• Goldstein AM, Tucker MA. Dysplastic nevi and melanoma. Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):528-32. doi: 10.1158/1055-9965.EPI-12-1346.

  PMID: 23549396 BACKGROUND

• Yang XR, Rotunno M, Xiao Y, Ingvar C, Helgadottir H, Pastorino L, van Doorn R, Bennett H, Graham C, Sampson JN, Malasky M, Vogt A, Zhu B, Bianchi-Scarra G, Bruno W, Queirolo P, Fornarini G, Hansson J, Tuominen R, Burdett L, Hicks B, Hutchinson A, Jones K, Yeager M, Chanock SJ, Landi MT, Hoiom V, Olsson H, Gruis N, Ghiorzo P, Tucker MA, Goldstein AM. Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations. Hum Genet. 2016 Nov;135(11):1241-1249. doi: 10.1007/s00439-016-1715-1. Epub 2016 Jul 23.

  PMID: 27449771 BACKGROUND

• Sargen MR, Pfeiffer RM, Elder DE, Yang XR, Goldstein AM, Tucker MA. The Impact of Longitudinal Surveillance on Tumor Thickness for Melanoma-Prone Families with and without Pathogenic Germline Variants of CDKN2A and CDK4. Cancer Epidemiol Biomarkers Prev. 2021 Apr;30(4):676-681. doi: 10.1158/1055-9965.EPI-20-1521.

  PMID: 33811164 DERIVED

• Sargen MR, Pfeiffer RM, Yang XR, Tucker MA, Goldstein AM. Variation in Cutaneous Patterns of Melanomagenesis According to Germline CDKN2A/CDK4 Status in Melanoma-Prone Families. J Invest Dermatol. 2020 Jan;140(1):174-181.e3. doi: 10.1016/j.jid.2019.06.138. Epub 2019 Jul 18.

  PMID: 31326397 DERIVED

• Tucker MA, Elder DE, Curry M, Fraser MC, Pichler V, Zametkin D, Yang XR, Goldstein AM. Risks of Melanoma and Other Cancers in Melanoma-Prone Families over 4 Decades. J Invest Dermatol. 2018 Jul;138(7):1620-1626. doi: 10.1016/j.jid.2018.01.021. Epub 2018 Feb 8.

  PMID: 29408205 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Melanoma; Dysplastic Nevus Syndrome; Skin Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Nevus; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Michael R Sargen, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Family Study Referrals

CONTACT

(800) 518-8474; ncifamilystudyreferrals@mail.nih.gov

Michael R Sargen, M.D.

CONTACT

(240) 276-7354; michael.sargen@nih.gov

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2002
• First Posted: June 26, 2002
• Study Start: July 1, 2002
• Last Updated: March 9, 2026

Record last verified: 2026-02-04

Locations

US (2)