Journal of the National Cancer Institute Advance Access originally published online on April 29, 2008
JNCI Journal of the National Cancer Institute 2008 100(9):663-671; doi:10.1093/jnci/djn101
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Published by Oxford University Press 2008.
ARTICLES |
Persistent Organochlorine Pesticides and Risk of Testicular Germ Cell Tumors
Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (KAM, SMQ, BIG); Toxicology Centre, Institut National de Sante Publique du Quebec, Quebec, QC (JPW); Army Medical Surveillance Activity, U.S. Army Center for Health Promotion and Preventive Medicine, Washington, DC (MVR); GEIS, Division of Preventive Medicine, Walter Reed Army Institute of Research, Silver Spring, MD (RLE)
Correspondence to: Katherine A. McGlynn, PhD, Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, EPS—Ste 550, 6120 Executive Blvd, Rockville, MD 20852-7234 (e-mail: mcglynnk{at}mail.nih.gov).
Background: Exposure to endocrine-disrupting chemicals, such as persistent organochlorine pesticides, has been suggested to increase the risk of testicular germ cell tumors (TGCTs).
Methods: To study the relationship of POP exposure to TGCT risk, prediagnostic serum samples from 754 case subjects and 928 control subjects enrolled in the Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study were analyzed for cis-nonachlor, trans-nonachlor, oxychlordane, total chlordanes, β-hexachlorocyclohexane, mirex, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyltrichloroethane. Adjusted odds ratios (ORs) and their associated 95% confidence intervals (CIs) for the risk of TGCT overall and for the histological subgroups, seminoma and nonseminoma, were estimated using multivariable logistic regression. All statistical tests were two-sided.
Results: TGCT risk was statistically significantly associated with higher plasma levels of p,p'-DDE (for highest quartile [Q4] vs lowest quartile [Q1], OR = 1.71, 95% CI = 1.23 to 2.38, Ptrend = .0002) and of two chlordane components, cis-nonachlor (Q4 vs Q1, OR = 1.56, 95% CI = 1.11 to 2.18, Ptrend = .009) and trans-nonachlor (Q4 vs Q1, OR = 1.46, 95% CI = 1.07 to 2.00, Ptrend = .026). Seminoma risk was statistically significantly associated with p,p'-DDE (Q4 vs Q1, OR = 1.91, 95% CI = 1.22 to 2.99, Ptrend = .0008), cis-nonachlor (Q4 vs Q1, OR = 1.93, 95% CI = 1.27 to 2.93, Ptrend = .0045), trans-nonachlor (Q4 vs Q1, OR = 1.72, 95% CI = 1.11 to 2.67, Ptrend = .033), and a chlordane metabolite, oxychlordane (Q4 vs Q1, OR = 1.64, 95% CI = 1.04 to 2.60, Ptrend = .048), whereas nonseminoma risk showed a statistically significant association with p,p'-DDE only (Q4 vs Q1, OR = 1.63, 95% CI = 1.10 to 2.42, Ptrend = .0044).
Conclusions: Increased exposure to p,p'-DDE may be associated with the risk of both seminomatous and nonseminomatous TGCTs, whereas exposure to chlordane compounds and metabolites may be associated with the risk of seminoma. Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these persistent organic pesticides during fetal life or via breast feeding may increase the risk of TGCT in young men.
| CONTEXT AND CAVEATS Prior knowledge Previous work had suggested that exposure to organochlorine pesticides was associated with increased risk of testicular germ cell tumors (TGCTs). Study design A case–control design was used to test the association of serum levels of several organochlorines and the risk of TGCTs in young men. Contribution The pesticide dichlorodiphenyldichloroethylene was statistically significantly associated with the risk of TGCTs, and the data suggested that chlordane isomers may be associated with the risk of seminoma. Implications Further examination of the association of organochlorine pesticides with TGCTs in other populations is needed, particularly given that more widespread use is being considered in the developing world. Limitations Because assessment of the association of several chemicals with TGCT risk entailed multiple comparisons, some of the results should be interpreted with caution.
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The authors wish to thank Emily Steplowski and Leslie Carroll of Information Management Services for their contributions in data management and analysis. The authors are also greatly indebted to the STEED participants, without whom there would have been no study. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
The authors take full responsibility for the study design, data collection, analysis and interpretation of the data, the decision to submit the manuscript for publication, and the writing of the manuscript.
Manuscript received October 4, 2007; revised February 17, 2008; accepted March 7, 2008.
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