Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00340873
Status:
COMPLETED
Last Update Posted:
2020-04-20
First Post:
2006-06-19
Brief Title:
Molecular Epidemiology of Dioxin-Related Illness in Seveso
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Molecular Epidemiology of Dioxin-Related Illness in Seveso
Status:
COMPLETED
Status Verified Date:
2020-04
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:
In 1976 an accidental explosion in a chemical plant 16 miles north of Milan resulted in contamination of the local population with 2 3 7 8-terachlorodibenzo-para-dioxin TCDD There is evidence that TCDD and related phenoxy herbicides act as teratogens tumor promoters and carcinogens in experimental animals In human TCDD causes chloracne in those exposed Associations with various cancers have been reported but the precise role in human toxicity immune and reproductive dysfunction and cancer is controversial
The Seveso accident provides a unique opportunity for an epidemiological investigation in that the exposures are the highest recorded in humans the exposure involves TCDD without other contaminants and a cohort in the involved and surrounding area has been enumerated
There is inter-individual variation in the action of genes involved in TCDD effect in human cells The quality of human AH receptor and the CYP1A1 and arnt genotypes are examples of susceptibility markers that may identify subjects at high risk for TCDD-related disease A hypothesis that could explain the inconsistent association of TCDD exposure with cancer is that genetic susceptibility may influence which individuals are adversely affected by TCDD exposure
The study is proceeding in three phases The first is a pilotvalidation study that is complete field activities and involved 126 subjects The second is a case-control study of about 100 individuals with chloracne and 100 controls The field components of phase one and two are complete and analyses of results are underway The third and final phase is a planned case-control study of TCDD-related cancers that will include approximately 125 cases and 125 controls
The study includes a questionnaireinterview and a biospecimen collection 73 ml of blood are obtained from each participant
The Seveso accident provides a unique opportunity for an epidemiological investigation in that the exposures are the highest recorded in humans the exposure involves TCDD without other contaminants and a cohort in the involved and surrounding area has been enumerated
There is inter-individual variation in the action of genes involved in TCDD effect in human cells The quality of human AH receptor and the CYP1A1 and arnt genotypes are examples of susceptibility markers that may identify subjects at high risk for TCDD-related disease A hypothesis that could explain the inconsistent association of TCDD exposure with cancer is that genetic susceptibility may influence which individuals are adversely affected by TCDD exposure
The study is proceeding in three phases The first is a pilotvalidation study that is complete field activities and involved 126 subjects The second is a case-control study of about 100 individuals with chloracne and 100 controls The field components of phase one and two are complete and analyses of results are underway The third and final phase is a planned case-control study of TCDD-related cancers that will include approximately 125 cases and 125 controls
The study includes a questionnaireinterview and a biospecimen collection 73 ml of blood are obtained from each participant
Detailed Description:
In 1976 an accidental explosion in a chemical plant 16 miles north of Milan resulted in contamination of the local population with 2 3 7 8-tetrachlorodibenzo-para-dioxin TCDD There is evidence that TCDD and related phenoxy herbicides act as teratogens tumor promoters and carcinogens in experimental animals In human TCDD causes chloracne in those exposed Associations with various cancers have been reported but the precise role in human toxicity immune and reproductive dysfunction and cancer is controversial
The Seveso accident provides a unique opportunity for an epidemiological investigation in that the exposures are the highest recorded in humans the exposure involves TCDD without other contaminants and a cohort in the involved and surrounding area has been enumerated
There is inter-individual variation in the action of genes involved in TCDD effect in human cells The quality of human AH receptor and the CYP1A1 and arnt genotypes are examples of susceptibility markers that may identify subjects at high risk for TCDD-related disease A hypothesis that could explain the inconsistent association of TCDD exposure with cancer is that genetic susceptibility may influence which individuals are adversely affected by TCDD exposure
The study is in three phases The first is a pilotvalidation study of 126 highly exposed and not exposed subjects The second is a case-control study of 100 individuals with chloracne and 100 controls The field components of phase one and two are complete The third and final phase is a planned case-control study of TCDD-related cancers that will include approximately 125 cases and 125 controls
Using different methods to estimate TCDD levels below the detection limit we found that approximately 20 years after the accident plasma TCDD was still elevated in subjects from the exposed areas particularly in women and was negatively associated with IgG plasma levels Subjects who developed chloracne after the accident had high TCDD levels and no evidence of TCDD-related long-term toxicity
The analyses of the expression of key genes in the aryl hydrocarbon receptor AhR pathway which is necessary for most TCDD effects showed a significant reduction in AhR expression by increasing plasma dioxin levels Cytochrome P450 gene SNPs and haplotypes were associated with variable TCDD-related gene inducibility
On-going studies are examining the proteomics and gene expression pattern by microarray in exposed subjects compared with not exposed individuals and the frerquency of t1418 translocations in lymphocytes from the same subjects
The study includes a questionnaireinterview and a biospecimen collection 73 ml of blood were obtained from each participant
The Seveso accident provides a unique opportunity for an epidemiological investigation in that the exposures are the highest recorded in humans the exposure involves TCDD without other contaminants and a cohort in the involved and surrounding area has been enumerated
There is inter-individual variation in the action of genes involved in TCDD effect in human cells The quality of human AH receptor and the CYP1A1 and arnt genotypes are examples of susceptibility markers that may identify subjects at high risk for TCDD-related disease A hypothesis that could explain the inconsistent association of TCDD exposure with cancer is that genetic susceptibility may influence which individuals are adversely affected by TCDD exposure
The study is in three phases The first is a pilotvalidation study of 126 highly exposed and not exposed subjects The second is a case-control study of 100 individuals with chloracne and 100 controls The field components of phase one and two are complete The third and final phase is a planned case-control study of TCDD-related cancers that will include approximately 125 cases and 125 controls
Using different methods to estimate TCDD levels below the detection limit we found that approximately 20 years after the accident plasma TCDD was still elevated in subjects from the exposed areas particularly in women and was negatively associated with IgG plasma levels Subjects who developed chloracne after the accident had high TCDD levels and no evidence of TCDD-related long-term toxicity
The analyses of the expression of key genes in the aryl hydrocarbon receptor AhR pathway which is necessary for most TCDD effects showed a significant reduction in AhR expression by increasing plasma dioxin levels Cytochrome P450 gene SNPs and haplotypes were associated with variable TCDD-related gene inducibility
On-going studies are examining the proteomics and gene expression pattern by microarray in exposed subjects compared with not exposed individuals and the frerquency of t1418 translocations in lymphocytes from the same subjects
The study includes a questionnaireinterview and a biospecimen collection 73 ml of blood were obtained from each participant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| OH95-C-N038 | None | None | None |