Carcinogenesis Advance Access originally published online on March 16, 2006
Carcinogenesis 2006 27(10):2001-2007; doi:10.1093/carcin/bgl011
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Published by Oxford University Press 2006
t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy
EPOCA Research Center for Occupational, Clinical and Environmental Epidemiology, Department of Occupational and Environmental Health, University of Milan and IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS Bethesda, MD, USA
2 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
*To whom correspondence should be addressed at: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, EPS 7114, Bethesda, MD 20892-7236, USA. Tel: +1 301 402 9519; Fax: +1 301 402 4489; Email: landim{at}mail.nih.gov
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 (2,3,7,8-tetrachlorodibenzo-p-dioxin) range: <1.7–475.0 parts per trillion (p.p.t.)] after the Seveso, Italy, accident of 1976. t(14;18) translocations were measured in DNA from peripheral blood lymphocytes by high-sensitivity real-time quantitative polymerase chain reaction. 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% confidence interval (CI), 2.9–6.2] in subjects with plasma TCDD < 10.0 p.p.t., 8.1 (95% CI, 4.9–13.3) in subjects with plasma TCDD between 10.0 and 50.0 and 12.5 (95% CI, 7.4–21.1) in subjects with plasma TCDD between 50.0 and 475.0 p.p.t. (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 (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 number 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.
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