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Carcinogenesis Advance Access first published online on March 16, 2006
This version published online on March 31, 2006
Carcinogenesis, doi:10.1093/carcin/bgl011
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Published by Oxford University Press 2006
Received November 28, 2005
Revised February 11, 2006
Accepted March 7, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy

Andrea Baccarelli 1, Carsten Hirt 2, Angela C. Pesatori 1, Dario Consonni 1, Donald G. Patterson Jr. 3, Pier Alberto Bertazzi 1, Gottfried Dölken 4, and Maria Teresa Landi 5 *

1 EPOCA Research Center for Occupational, Clinical, and Environmental Epidemiology, Department of Occupational and Environmental Health, University of Milan, Milan, Italy
2 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA; Department of Hematology and Oncology, University Medical Center, Ernst-Moritz-Arndt-University, Sauerbruchstrasse, D-17487 Greifswald, Germany
3 Division of Environmental Health Laboratory Science, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
4 Department of Hematology and Oncology, University Medical Center, Ernst-Moritz-Arndt-University, Sauerbruchstrasse, D-17487 Greifswald, Germany
5 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA

* To whom correspondence should be addressed.
Maria Teresa Landi, E-mail: landim{at}mail.nih.gov


  Abstract

Dioxin exposure has been associated with Non-Hodgkin's Lymphoma (NHL) in epidemiological investigations. The NHL-related t(14;18) translocations can be detected at a low copy number in lymphocytes from healthy subjects. Exposure to NHL-associated carcinogens, such as dioxin or pesticides, may cause expansion of t(14;18)-positive clones. We investigated prevalence and frequency of circulating t(14;18)-positive lymphocytes in 144 healthy subjects from a population exposed to dioxin (plasma TCDD range: <1.7-475.0 ppt) after the Seveso, Italy accident of 1976. t(14;18) was measured in DNA from peripheral blood lymphocytes by high-sensitivity Real-Time Quantitative PCR. We found that the frequency, but not the prevalence, of t(14;18) translocation-positive cells increased with increasing plasma TCDD. Among t(14;18)-positive subjects (n=50; 34.7%), the mean number of t(14;18) translocations/106 lymphocytes was 4.2 (95%CI 2.9-6.2) in subjects with plasma TCDD<10.0 ppt, 8.1 (95%CI 4.9-13.3) in subjects with plasma TCDD between 10.0-50.0 ppt, and 12.5 (95%CI 7.4-21.1) in subjects with plasma TCDD between 50.0-475.0 ppt (p-trend=0.003). As expected, t(14;18) frequency was associated with cigarette smoking and was highest in subjects who smoked for 16 years or more (mean=12.6, 95% CI 7.4-21.3, p=0.01). Higher t(14;18) prevalence was found among individuals with fair hair color (p=0.01) and light eye color (p=0.04). No significant association between t(14;18) and age was found. Our results show that dioxin exposure is associated with increased numbers of circulating t(14;18) positive cells. Whether this change in t(14;18) frequency is an indicator of elevated lymphoma risk remains speculative and needs further investigation for its potential impact on public health.

Keywords: Translocations; Dioxin; Seveso; Epidemiology; Lymphoma.
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