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

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 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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Available from: Dana B Barr, Sep 28, 2015
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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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    ABSTRACT: Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance and may exert adverse consequences on humans. The male reproductive system may be susceptible to the effects of such environmental toxicants. This review discusses the recent progress in scientific data mainly from epidemiology studies on the associations between EDCs and male reproductive health and our understanding of possible mechanisms associated with the effects of EDCs on male reproductive health. Finally, the review provides recommendations on future research to enhance our understanding of EDCs and male reproductive health. The review highlights the need for (1) well-defined longitudinal epidemiology studies, with appropriately designed exposure assessment to determine potential causal relationships; (2) chemical and biochemical approaches aimed at a better understanding of the mechanism of action of xenoestrogens with regard to low-dose effects, and assessment of identify genetic susceptibility factors associated with the risk of adverse effects following exposure to EDCs.
    Frontiers in Public Health 06/2014; 2:55. DOI:10.3389/fpubh.2014.00055
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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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    ABSTRACT: Testicular germ cell tumours (TGCT) are the most common cancers in men aged between 15 and 44 years and the incidence has increased steeply over the past 30 years. The rapid increase in the incidence, the spatial variation and the evolution of incidence in migrants suggest that environmental risk factors play a role in TGCT aetiology. The purpose of our review is to summarise the current state of knowledge on occupational and environmental factors thought to be associated with TGCT. A systematic literature search of PubMed. All selected articles were quality appraised by two independent researchers using the 'Newcastle-Ottawa Quality Assessment Scale'. After exclusion of duplicate reports, 72 relevant articles were selected; 65 assessed exposure in adulthood, 7 assessed parental exposures and 2 assessed both. Associations with occupation was reported for agricultural workers, construction workers, firemen, policemen, military personnel, as well as workers in paper, plastic or metal industries. Electromagnetic fields, PCBs and pesticides were also suggested. However, results were inconsistent and studies showing positive associations tended to had lower quality ranking using the assessment scale (p=0.02). Current evidence does not allow concluding on existence of any clear association between TGCT and adulthood occupational or environmental exposure. The limitations of the studies may partly explain the inconsistencies observed. The lack of association with adulthood exposure is in line with current hypotheses supporting the prenatal origin of TGCT. Future research should focus on prenatal or early life exposure, as well as combined effect of prenatal and later life exposure. National and international collaborative studies should allow for more adequately powered epidemiological studies. More sophisticated methods for assessing exposure as well as evaluating gene-environment interactions will be necessary to establish clear conclusion.
    PLoS ONE 10/2013; 8(10):e77130. DOI:10.1371/journal.pone.0077130 · 3.23 Impact Factor
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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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    ABSTRACT: In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.
    Frontiers in Endocrinology 11/2012; 3:150. DOI:10.3389/fendo.2012.00150
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