Identifying Gene Mutations in Patients With Melanoma and in Families With a History of Hereditary Melanoma
Studies of Familial Melanoma
RATIONALE: Identifying gene mutations and other risk factors in patients with melanoma and in families with a history of hereditary melanoma may help doctors identify persons at risk for melanoma and other types of cancer. It may also help the study of cancer in the future.
PURPOSE: This clinical trial is studying gene mutations in patients with melanoma and in families with a history of hereditary melanoma.
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
- Determine the incidence and etiologic significance of variants of known melanoma susceptibility genes (MSGs) in families with multiple cases of melanoma.
- Determine the proportion of multiple-case families that are explained by high-penetrance mutations in known MSGs.
- Determine the proportion of multiple-case families that are explained by these mutations and whether it varies with latitude, as a surrogate for ultraviolet exposure, with number of affected relatives, with average age at onset of melanoma in relatives, with presence of multiple primary melanoma, or with other family-specific variables.
- Determine the penetrance of MSG mutations in these families.
- Determine if the penetrance varies with age, sex, or birth cohort.
- Determine if the penetrance varies with the gene involved or nature of the mutation.
- Assess the penetrance in mutations that also have a deleterious effect on the alternative splice product, p14ARF.
- Determine whether carriers of MSGs have an increased susceptibility to other types of cancer.
- Determine the risk of other types of cancers for mutation carriers.
- Determine environmental exposures, in particular sun exposure, that modify risk of melanoma in MSG mutation carriers.
- Determine the cutaneous phenotypes that correlate with melanoma risk in these families.
- Correlate cutaneous phenotypes with the presence of MSG variants.
- Determine the effect of other covariates, such as sun exposure or the presence of alleles of putative modifying genes (e.g., MC1R or CDKN2A), on phenotype.
- Determine if modifier genes, such as those controlling pigmentation of the skin, and therefore sun susceptibility, modify risk in MSG mutation carriers.
- Identify any histopathological correlates of MSG status in primary tumors arising in melanoma-susceptible individuals in these families.
- Identify any histopathological correlates of primary melanomas in carriers of MSG mutations with other covariates.
OUTLINE: This is a case-control, multicenter study.
Participants complete 2 questionnaires and assist in the creation and expansion of a family pedigree. Blood samples are examined for melanoma susceptibility gene mutations, including CDK4 and CDKN2A.
Participants are also examined for moles and photographed. Physical variables (e.g., skin, eye, and hair pigmentation) and sun damage (solar lentigines and freckling) are also noted.
If available, tissue samples are examined for Clark level, Breslow thickness, and frequency of mitoses. Peri-lesional skin from tumors is examined by p53 staining.
Participants are followed periodically to monitor cancer development.
Peer reviewed and funded or endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 5,000 participants will be accrued for this study.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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England
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Leeds, England, United Kingdom, LS9 7TF
- Recruiting
- Leeds Cancer Centre at St. James's University Hospital
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Contact:
- Julia Newton Bishop, MD
- Phone Number: 44-113-206-4668
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Meets one of the following criteria:
Prior multiple primary melanomas
- Histological samples available
- Family history of melanoma, with melanoma in two first-degree relatives (e.g., cases of melanoma in both a mother and son or in two brothers but not in two cousins)
- Family history of melanoma, where three or more individuals (of any relationship) have had melanoma
PATIENT CHARACTERISTICS:
- Not specified
PRIOR CONCURRENT THERAPY:
- Not specified
Study Plan
How is the study designed?
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Predictive significance of melanoma susceptibility gene (MSG) mutations in the CDKN2A gene
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Susceptibility to other types of cancer as a feature of MSG mutations
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Risk of other types of cancers in mutation carriers
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Environmental exposures, in particular sun exposure, that modify risk of melanoma in MSG mutation carriers
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Collaborators and Investigators
Investigators
- Study Chair: Julia Newton Bishop, MD, Leeds Cancer Centre at St. James's University Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CRUK-LCC-99/3/45
- CDR0000532941 (Registry Identifier: PDQ (Physician Data Query))
- EU-20705
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