Ignite Creation Date:
2024-05-05 @ 4:53 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00339222
Status:
COMPLETED
Last Update Posted:
2020-07-01
First Post:
2006-06-19
Brief Title:
Family Study of Melanoma in Italy
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Family Study of Melanoma in Italy
Status:
COMPLETED
Status Verified Date:
2020-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 genes 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 eg 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 patients 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
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 genes 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 eg 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 patients 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
Detailed Description:
To date 557 subjects including cases of melanoma and unaffected relatives have been recruited in the family study of melanoma at the Bufalini Hospital Cesena Italy University oflAquila LAquila 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 genes 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- N35 Finally some families with three or more affected individuals are ongoing exomic sequencing with the goal of identifying novel loci associated with melanoma susceptibility More than 100 subjects have been sequenced to date We have identified a potentially important candidate gene for melanoma and are investigating additional families and melanoma cases to verify whether we can replicate this finding
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
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 genes 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- N35 Finally some families with three or more affected individuals are ongoing exomic sequencing with the goal of identifying novel loci associated with melanoma susceptibility More than 100 subjects have been sequenced to date We have identified a potentially important candidate gene for melanoma and are investigating additional families and melanoma cases to verify whether we can replicate this finding
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-C-N038 | None | None | None |