ZIA CP101231 08278 (ZIA) | |||
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Title | Molecular epidemiology of dioxin-related illness in Seveso | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Landi, Maria Teresa | NCI Program Director | N/A |
Cancer Activity | N/A | Division | DCEG |
Funded Amount | $642,632 | Project Dates | null - null |
Fiscal Year | 2018 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Agent Orange/Dioxin Related (100.0%) Biochemical Epidemiology (45.0%) Cancer (100.0%) |
N/A | ||
Research Type | |||
Exogenous Factors in the Origin and Cause of Cancer Interactions of Genes and/or Genetic Polymorphisms with Exogenous and/or Endogenous Factors |
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Abstract | |||
In 1976 an accidental explosion in a chemical plant in Seveso, Italy 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 humans, TCDD causes chloracne but the precise role in immune and reproductive dysfunction, and cancer is controversial. Approximately 20 years after the Seveso, Italy accident we designed a population-based study to evaluate the impact of TCDD exposure on chloracne and cancer using mechanistically-based biomarkers of dioxin response in humans. We measured current lipid-adjusted plasma TCDD concentrations in these subjects, and found they were still elevated in exposed subjects, particularly in women, and were inversely associated with plasma IgG. Subjects who developed chloracne after the accident had no evidence of dioxin-related long-term toxicity. Using improved methods to estimate dioxin levels, we identified several changes in gene expression in lymphocytes and increased frequency of t(14;18) translocation-positive cells with increasing plasma dioxin. We also found that maternal dioxin exposure affects neonatal thyroid function. |