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

Abstract

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 chromatographyhigh-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 z23 repeats) or GGN (<17 versus z17 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. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2012 -8)

Effect of endogenous and exogenous hormones on testicular cancer: the epidemiological evidence

“…Biggs et al, (2008) found no evidence that the risk of TC was associated with serum DDE. Recently, a hospital-based case-control study conducted in Italy found that TC patients had elevated concentrations of p,p -DDE (Giannandrea et al, 2011).…”

“…Only one study has examined whether the TC risk associated with hormonally active compounds was modified by androgen receptor CAG. It found no evidence that the risk of TC associated with p,p'-DDE was modified by the number of CAG repeats (Biggs et al, 2008). Several published case-control studies found that longer CAG repeats were associated with risk of nonseminoma.…”

“…The fungicide HCB has been assessed in three studies in relation to TC but none have found evidence for association (Hardell et al, 2003;Biggs et al, 2008;Purdue et al, 2009). Only one study has assessed maternal HCB in relation to TC (Hardell et al, 2003).…”

Pre-Diagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors

“…In addition, the case mothers in that study had significantly higher levels of cis-nonachlor, trans-nona chlor, and the sum of chlordanes compared with control mothers, suggesting that the ante natal period may be a particularly important time window of exposure for influencing TGCT development. No associations with chlordane congeners were observed in the Washington State study (Biggs et al 2008). The biologic basis for a chlordane effect on TGCT develop ment is unclear.…”

“…The U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinant (STEED) Study, a large case-control investigation of TGCTs (754 cases, 928 controls) conducted among U.S. servicemen, similarly found elevated prediagnostic concentrations of cis-nonachlor, trans-nonachlor, and the insecticide metabolite p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) among cases versus controls (McGlynn et al 2008). However, a recent population-based study (246 cases, 630 controls) conducted in Washington State observed no evidence of association with OC compounds (Biggs et al 2008). Findings from studies of cryptorchidism and hypospadias do not support an association with OC compounds (Bhatia et al 2005;Damgaard et al 2006;Flores-Luevano et al 2003;Longnecker et al 2002;Waliszewski et al 2005).…”