Family Study of Melanoma in Italy

This study is currently recruiting participants.
Verified June 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00339222
First received: June 19, 2006
Last updated: March 14, 2014
Last verified: June 2013
  Purpose

During the course of a case-control study of melanoma conducted at the Bufalini Hospital, Cesena, Italy in the years 1994-1996, 20 families with 2 or 3 melanoma cases were identified and studied. The area where the study was conducted showed the steepest increase in melanoma incidence in Mediterranean populations between the years 1987 and 1997.

Clinical characteristics of melanoma in the families studied were similar to those typically described in fair-skinned populations, but no relevant mutations in the coding regions of known candidate genes from melanoma have been found. Lack of findings could be due to the modest number of families and the small number of affected CMM cases examined. We cannot exclude the possibility of alterations in introns, splicing sites or promoter regions. Also epigenetic factors could affect the expression of the gene products we studied. Alternatively, germline alterations of a gene(s) other than the candidate genes we analyzed may play an important role in melanoma predisposition in this population. A large number of families is needed to test these hypotheses.

These additional families could provide an important contribution to the understanding o melanoma development. In fact, this population does not generally have the host characteristics that are usually associated with higher risk for melanoma (e.g., light skin color, red hair, blue eyes, multiple freckles, tendency to sunburn, etc.) but do have a relative high frequency of dysplastic nevi and melanoma.

The main objective of this study is to recruit more families at the Bufalini Hospital, Cesena, Italy in order to reach a larger sample size. Recently, 16 potential melanoma-prone families have been identified through patient's or physicians' referrals by the Dermatologists at the Bufalini Hospital. The dermatologists have maintained close relationships with members of these families and are confident that these subjects would be willing to participate in a study if contacted. The first goal of our study is to contact this family group and verify their willingness to participate in the study. In addition, new families could be identified and recruited.

We propose to conduct a pilot project. We estimate recruitment of approximately 25 families with 2 or more melanoma cases in first -degree relatives over a one-year period, including the 16 families already identified and approximately 10 new kindreds. At the end of the pilot phase we will determine the feasibility of continuing recruitment.


Condition
Melanoma

Study Type: Observational
Official Title: Family Study of Melanoma in Italy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 600
Study Start Date: November 2001
Detailed Description:

To date 457 subjects, including cases of melanoma and unaffected relatives, have been recruited in the family study of melanoma at the Bufalini Hospital, Cesena, Italy, University ofl'Aquila, L'Aquila, Italy, and the Istituto Valenciano de Oncologia, Valencia, Spain. Clinical characteristics of melanoma in the families studied were similar to those typically described in fair-skinned populations. In the original study from the Bufalini Hospital, only 7% of the families analyzed have been shown to carry mutation in the CDKN2A gene, known candidate gene for melanoma, and no other mutation in additional susceptibility genes have been identified. The possibility of alterations in introns, splicing sites, or promoter regions cannot be excluded. Also, epigenetic factors could affect the expression of the gene products we studied. Alternatively, germline alterations of a gene(s) other than the candidate genes may play an important role in melanoma predisposition in this population. We began genome-wide scanning of the first 47 families. There was no evidence for linkage to either chromosome 9 or chromosome 1, previously shown to be susceptibility loci for melanoma. We extended the samples size also including melanoma-prone families from other Italian investigators. We have performed fine mapping of the loci that appeared interesting in the first linkage analysis. We did not confirm the previous association with the disease and published a manuscript to report the null results. Some of these families were also analyzed together with other families worldwide in linkage and genome-wide association studies with the goal of identifying loci potentially important for melanoma etiology. Moreover, some individuals from this study are being analyzed for presence of variants in susceptibility genes in pigmentation, DNA repair, and other pathways together with the melanoma samples from the case-control study (02-C- N(35). Finally, some families with three or more affected individuals are ongoing exomic sequencing with the goal of identifying novel loci associated with melanoma susceptibility.

This protocol proposes to continue recruitment of families in order to reach a larger sample size for future analysis. The additional families could provide an important contribution to the understanding of melanoma development.

In addition, this protocol proposes to continue recruiting subjects for the tissue study subgroup at the Bufalini Hospital of Cesena, the Unviersity of I' Aquila, Italy and the Istituto Valenciano de Oncologia, Valencia, Spain. To date, 98 subjects have been enrolled in this study. The study aims at investigating the progression from nevi to melanoma in a cross sectional study of melanoma cases. The tissue study component focuses on the comparison of gene expression, somatic mutations, genetic variants, and proteomics profile in normal skin, common melanocytic nevi, dysplastic nevi, and melanoma tissue samples from the same individuals (familial or sporadic cases). Each subject completes an interview based questionnaire on sun exposure, pigmentation, sunsensitivity, family and medical history, and other melanoma risk factors and donates a blood sample.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Individuals with the diagnosis of CMM at the Department of Dermatology, Bufalini Hospital, Cesena, Italy who have other family members affected with CMM will be eligible for participation.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00339222

Contacts
Contact: Maria T Landi, M.D. (301) 402-9519 landim@mail.nih.gov

Locations
Italy
Bufalini Hospital Cesena, Italy Recruiting
Cesena, Italy, 00/00/00
Contact: Calista Donato, M.D.    Not Listed      
Sponsors and Collaborators
Investigators
Principal Investigator: Maria T Landi, M.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00339222     History of Changes
Obsolete Identifiers: NCT00556829
Other Study ID Numbers: 999902038, 02-C-N038
Study First Received: June 19, 2006
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Genetics
Kindreds
Mediterranean Population
Nevi
Pigmentation
Melanoma-Prone Families
Sun Exposure
Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 23, 2014