Serum Organochlorine Pesticide Residues and Risk of Testicular Germ Cell Carcinoma: A Population-Based Case-Control Study

Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Box 354922, Seattle, WA 98195-4922, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 08/2008; 17(8):2012-8. DOI: 10.1158/1055-9965.EPI-08-0032
Source: PubMed


Testicular germ cell carcinoma (TGCC) is the most common malignancy among men ages 20 to 34 years. Although the pathogenesis of TGCC is poorly understood, suboptimal androgen levels or impaired androgen signaling may play a role. Some persistent organochlorine pesticides commonly found in human tissue possess antiandrogenic properties. We examined whether the risk of TGCC is associated with serum levels of 11 organochlorine pesticides, including p,p'-DDE, and whether the p,p'-DDE-TGCC association is modified by CAG or GGN repeat polymorphisms in the androgen receptor gene. We conducted a population-based case-control study among 18- to 44-year-old male residents of three Washington State counties. Cases (n = 246) were diagnosed during 1999 to 2003 with a first, primary TGCC. Controls (n = 630) were men of similar age with no history of TGCC from the same population identified through random-digit telephone dialing. Questionnaires elicited information on demographic, medical, and lifestyle factors. A blood specimen provided serum for gas chromatography-high-resolution mass spectrometry analysis of organochlorine pesticide residues and DNA for genotyping. We observed no clear patterns between TGCC risk and concentrations of any of the organochlorines measured, nor did we observe that the risk associated with p,p'-DDE was modified by androgen receptor CAG (<23 versus > or =23 repeats) or GGN (<17 versus > or =17 repeats) genotype. This study does not provide support for the hypothesis that adult exposure to organochlorine pesticides is associated with risk of TGCC. Due to uncertainty regarding how well organochlorine levels measured in adulthood reflect exposures during early life, further research is needed using exposure measurements collected in utero or during infancy.

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    • "Subjects in the highest serum p,p′-DDE quartile (>0.390 μg/g lipid) compared to those in the first serum p,p′-DDE quartile (0.157 μg/g lipid) supported increased risk of TGCT in relation to exposure to DDE and PCBs (78). On the other hand, DDE was not associated with TGCT in a case–control study of 876 adult men in Washington State, U.S. (79). Finally, several small studies have suggested an association between PCB exposure and prostate cancer (80, 81), whereas no association was reported between PCBs and prostate cancer in a recent Canadian study of 79 cases and 329 age frequency matched controls (82). "
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    • "McGlynn et al. reported a protective effect for PCBs serum levels, either individually or grouped [29], while others studies showed mixed effects (increased or decreased risk) [79], or no association [19]. However, some authors suggest there is uncertainty on the conclusions to be drawn from observed association between organochlorine levels measured in adulthood and past exposures occurred during early (or prenatal) life since important physiological variations occur over life, especially at puberty [78]. Moreover, exposure may have occurred after the in utero or infancy period and genetic polymorphisms in metabolism may also have an impact on the serum concentrations [27]. "
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    • "Next to this, as TC development seems to be either associated with genetic predisposition and or environmental exposure, it might be of interest to analyze the potential combination of such anomalies. Consistent with this hypothesis, as polymorphisms in AR and some organochlorine pesticides have been associated to risk of TGCC development, and that some of these organochlorine pesticides present anti-androgenic activities, Biggs et al. (2008) have studied the potential interaction of AR polymorphisms and exposure to p,p′-DDE and the association with TC risk. According to their study, they were not able to demonstrate any association between p,p′-DDE exposure and TC risk, either or not in combination with (CAG)n length. "
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