Fertility and prognosis assessment between bleomycin/etoposide/cisplatin and paclitaxel/carboplatin chemotherapy regimens in the conservative treatment of malignant ovarian germ cell tumors: a multicenter and retrospective study.

OBJECTIVE: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). METHODS: A propensity score matching algorithm was performed between the BEP and PC groups. The χ² test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. RESULTS: We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8-44 years), and the median follow-up period was 63 months (range, 2-191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. CONCLUSION: The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis.

An overview of chemotoxicity and radiation toxicity in cancer therapy.

While immunotherapy and targeted therapies represent major advances against different types of malignancies, the mainstay of cancer therapy continues to be radiation and surgery for localized disease, and chemotherapy for systemic disease, with the preponderance of chemotherapeutic agents (such as anthracyclines, alkylating agents, and antimetabolites) having been developed decades ago. Combination chemotherapy regimens have changed the natural history of once deadly diseases such as breast and prostate cancer and led to curative regimens in advanced hematological malignancies and testicular cancer. However, while oncologists maintain their focus on disease suppression, and where feasible, disease eradication, obstacles to achieving cure remain, such as tumor dormancy and ultimately disease recurrence, as well as both intrinsic and acquired resistance. In this review, complications of current cancer therapies toward major organs (heart, lung, kidney, gastro-intestinal, neuromuscular, brain, and skin) are emphasized, and efforts to mitigate these complications are described. This is particularly relevant for patients treated with curative intent, where adherence to treatment plan, and avoidance of interruptions in treatment schedule are essential for optimal outcome. Consequently, these patients are treated with an "aggressive" approach, with high tolerance for side effects. However, a deeper understanding of normal tissue toxicity resulting from the different cancer therapies remains an area of unmet medical need that will ultimately lead to improved therapeutic index for current and future therapies, planning for treatment adverse effects, and ultimately improvement in patient satisfaction, compliance and outcome.

Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study.

BACKGROUND: Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. METHODS: We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. CONCLUSIONS: Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

Exposure to ambient dichloromethane in pregnancy and infancy from industrial sources and childhood cancers in California.

BACKGROUND: The incidence of childhood cancers has been increasing and environmental exposure to air toxics has been suggested as a possible risk factor. This study aims to explore ambient exposure to dichloromethane (methylene chloride). METHODS: We frequency matched by birth year approximately 20 cancer-free controls identified from birth records to all childhood cancers ages 0-5 in the California Cancer Registry diagnosed from 1988 to 2012; i.e. 13,636 cases and a total of 270,673 controls. Information on industrial releases of dichloromethane within 3km of birth addresses was retrieved from mandatory industry reports to the EPA's Toxics Release Inventory (TRI). We derived exposure to dichloromethane within close vicinity of birth residences using several modeling techniques including unconditional logistic regression models with multiple buffer distances, inverse distance weighting, and quadratic decay models. RESULTS: We observed elevated risks for germ cell tumors [Odds Ratio (OR): 1.52, 95% Confidence Interval (CI) 1.11, 2.08], particularly teratomas (OR: 2.08, 95% CI 1.38-3.13), and possible increased risk for acute myeloid leukemias (AML) (OR: 1.64, 95% CI 1.15-2.32 in the quadratic decay model). Risk estimates were similar in magnitude whether releases occurred in pregnancy or the child's first year of life. CONCLUSION: Our findings suggest that exposure to industrial dichloromethane releases may be a risk factor for childhood germ cell tumors, teratomas, and possibly AML.

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer.

During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can explain this development. This review focuses on the hypothesis that testicular germ cell cancer, which originates from germ cell neoplasia in situ, is of foetal origin and associated with other male reproductive problems through a testicular dysgenesis syndrome, also including foetal origin of impaired spermatogenesis, hypospadias and cryptorchidism. There is little doubt that environmental factors associated with modern lifestyles have - in a broad sense - had an adverse influence on male reproductive health. The hypothesis that exposure to endocrine-disrupting chemicals plays a fundamental role in this trend is plausible. This is based on evidence from animal studies that demonstrate adverse reproductive effects caused by a number of endocrine-disrupting chemicals to which humans are exposed as part of our modern lifestyle.

Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis.

BACKGROUND: The aetiology of testicular cancer remains elusive. In this manuscript, we review the evidence regarding the association between cannabis use and testicular cancer development. METHODS: In this systematic review and meta-analysis, we reviewed literature published between 1(st) January 1980 and 13(th) May 2015 and found three case-control studies that investigated the association between cannabis use and development of testicular germ cell tumours (TGCTs). RESULTS/CONCLUSIONS: Using meta-analysis techniques, we observed that a) current, b) chronic, and c) frequent cannabis use is associated with the development of TGCT, when compared to never-use of the drug. The strongest association was found for non-seminoma development--for example, those using cannabis on at least a weekly basis had two and a half times greater odds of developing a non-seminoma TGCT compared those who never used cannabis (OR: 2.59, 95% CI 1.60-4.19). We found inconclusive evidence regarding the relationship between cannabis use and the development of seminoma tumours. It must be noted that these observations were derived from three studies all conducted in the United States; and the majority of data collection occurred during the 1990's.

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

INTRODUCTION: Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders. PURPOSE: To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU). METHODS: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources. RESULTS: The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion. CONCLUSIONS: EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.

Studying the impact of early life exposures to pesticides on the risk of testicular germ cell tumors during adulthood (TESTIS project): study protocol.

BACKGROUND: The incidence of testicular germ cell tumors (TGCT), the most common cancer in men aged 15 to 45 years, has doubled over the last 30 years in developed countries. Reasons remain unclear but a role of environmental factors, especially during critical periods of development, is strongly suspected. Reliable data on environmental exposure during this critical time period are sparse. Little is known on whether it could be a combined effect of early and later-life exposures. METHODS/DESIGN: Our research aims to study the association between TGCT risk and pesticide exposures (domestic, occupational and environmental) during critical time periods of development and combined early and later-life exposures. The study design, developed during a 2-year pilot study, is a multicenter case-control study of 500 cases (ascertained through histology) and 1000 fertile/fecund controls recruited through 21 French 'Centres d'Etude et de Conservation des Œufs et de Sperme humain' (CECOS). Trained professional interviewers interview the subjects and their mothers by phone. Using a geographic information system developed and tested for application in this study design, environmental pesticides exposure assessment is based on life-time residential history. Occupational pesticides exposures are assessed by an industrial hygienist based on parents' occupations and tasks. Exposures during the prenatal period, early childhood and puberty are focused. A blood sample is collected from each participant to assess genetic polymorphisms known to be associated with TGCT risk, as well as to explore gene-environment interactions. DISCUSSION: The results of our study will contribute to better understanding the causes of TGCT and the rapid increase of its incidence. We explore the effect of combined early and later-life pesticides exposure from multiple sources, as well as potential gene-environment interactions that have until now been rarely studied for TGCT. Our design allows future pooled studies and the bio-bank allows additional genetic or toxicological analyses.

Positron emission tomography (PET) is not indicated in the postchemotherapy evaluation of advanced non-seminomatous testicular germ cell tumors

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[Testicular germ cell tumours and early exposures to pesticides: The TESTEPERA pilot study]. / Tumeurs germinales du testicule et expositions précoces aux pesticides : étude pilote TESTEPERA.

Testicular germ cell tumors (TGCT) represent the most frequent cancer in men aged between 15 and 45 years. Current hypotheses are focusing on environmental exposures occurring during prenatal periods. However, very few studies have explored intra-uterine environmental exposure related to TGCT. TESTEPERA is a pilot case-control study aiming to determine the effectiveness of different recruitment approaches in the French context and to verify our ability to collect relevant data on their prenatal periods. Between 2011 and 2012, 150 male subjects were contacted in the Rhône-Alpes region (58 cases from a cancer center and 92 controls from a regional maternity). Participation rate varied from 33% for cases diagnosed in 2008 vs 68% for cases diagnosed in 2010. Participation rate of controls varied depending on modalities of contact (13% for face-to-face recruitment; 0% for contact by phone only; 50% for face-to-face contact with phone reminder). Data collection allowed precise job identification and geolocation of subjects' addresses. Precision of geolocation was dependent upon the level of urbanization (p < 0.001) but not on the time period (p = 0.52). Our results support the feasibility of a case-control study focusing on the relation between TGCT and environmental pesticide exposures during early and later life.

Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells.

Although testicular germ cell tumors are generally quite responsive to treatment with cisplatin, a small fraction of them acquire resistance during therapy. Even when cisplatin treatment is successful the patient is often left with a residual teratoma at the site of the primary tumor suggesting that cisplatin may trigger differentiation in some tumors. Using the human embryonal carcinoma cell line NTera2/D1, we confirmed that exposure to the differentiating agent retinoic acid produced a reduction in pluripotency markers NANOG and POU5F1 (Oct3/4) and an acute concentration-dependent increase in resistance to both cisplatin and paclitaxel that reached as high as 18-fold for cisplatin and 61-fold for paclitaxel within four days. A two day exposure to cisplatin also produced a concentration-dependent decrease in the expression of the NANOG and POU5F1 and increased expression of three markers whose levels increase with differentiation including Nestin, SCG10 and Fibronectin. In parallel, exposure to cisplatin induced up to 6.2-fold resistance to itself and 104-fold resistance to paclitaxel. Paclitaxel did not induce differentiation or resistance to either itself or cisplatin. Neither retinoic acid nor cisplatin induced resistance in cervical or prostate cancer cell lines or other germ cell tumor lines in which they failed to alter the expression of NANOG and POU5F1. Forced expression of NANOG prevented the induction of resistance to cisplatin by retinoic acid. We conclude that cisplatin can acutely induce resistance to itself and paclitaxel by triggering a differentiation response in pluripotent germ cell tumor cells.

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

Testicular cancer is the most common type of malignancy in men aged 15-40 years. Although its incidence has increased over the past 40 years in most countries, the reasons for this rise are unclear. It has been suggested that a relative excess of endogenous estrogens during prenatal life and/or later exposures to various occupational and environmental estrogenic chemicals such as organochlorine compounds may play a causal role in the etiology of testicular cancer, but the issue is still open to further research. The purpose for this review is to summarize the epidemiologic literature about hormonal factors, endogenous hormones and environmental xenoestrogens, and testicular carcinogenesis. Future studies need to (a) consider the possible synergistic effect of exposure to environmental xenoestrogens and sex hormones, (b) focus on the most vulnerable life stages of exposure to endocrine disruptors and testicular cancer risk, (c) assess the possible additive role of androgen secretion occurring during puberty in tumor progression, and (d) consider more systematically gene-environment interactions.

Exposure to metal-working fluids in the automobile industry and the risk of male germ cell tumours.

INTRODUCTION: In a previous analysis of a case-control study of testicular cancer nested in a cohort of automobile workers, we observed an increased risk for testicular cancer among workers who had ever been involved in occupational metal-cutting tasks. We investigated whether this risk increase was due to exposure to metal-working fluids (MWF). METHODS: Occupational exposure to MWF was assessed in detail using a job-specific questionnaire for metal-cutting work. We calculated ORs and associated 95% CIs individually matched for age (±2 years) and adjusted for a history of cryptorchidism by conditional logistic regression. RESULTS: The prevalence of exposure to MWF was 39.8% among cases and 40.1% among controls. For total germ cell tumours and seminomas we did not observe risk increases for metal-cutting tasks or occupational exposure to MWF (OR 0.95; 95% CI 0.69 to 1.32 and OR 0.88; 95% CI 0.58 to 1.35, respectively). However, dermal exposure to oil-based MWF was associated with an increased risk for non-seminomatous testicular cancer. Dermal exposure to oil-based MWF for more than 5000 h showed particularly high risk estimates (OR 4.72; 95% CI 1.48 to 15.09). DISCUSSION: Long-term dermal exposure to oil-based MWF was a risk factor for the development of non-seminomatous testicular germ cell cancer. Possible measures to reduce exposure include the introduction of engineering control measures such as venting or enclosing of machines, and enforcing the use of personal protective equipment during metal cutting.

The MDM2-a splice variant of MDM2 alters transformation in vitro and the tumor spectrum in both Arf- and p53-null models of tumorigenesis.

MDM2-A is a common splice variant of murine double minute 2 (MDM2) that is frequently detected in many tumor types. Our previous work has characterized MDM2-A as an activator of p53, and therefore, in a wild-type p53 background, this splice variant would be predicted to confer p53-dependent tumor protection. To test this hypothesis, we used Mdm2-a transgenic mice to assess transformation and tumorigenesis in tumor susceptible murine models. A MDM2-A-dependent decrease in transformation was observed in Arf-null mouse embryonic fibroblasts (MEF) or when wild-type MEFs were exposed to the carcinogen ethylnitrosourea. However, this reduced transformation did not confer tumor protection in vivo; Mdm2-a/Arf-null mice and ethylnitrosourea-treated MDM2-expressing mice developed similar tumor types with equivalent latency compared with their respective controls. Interestingly, when p53 was deleted, MDM2-A expression enhanced transformation of p53-null MEFs and altered tumor spectrum in vivo. In addition, p53-heterozygous mice that expressed MDM2-A developed aggressive mammary tumors that were not observed in p53-heterozygous controls. In conclusion, we found that although MDM2-A expression enhances p53 activity and decreases transformation in vitro, it cannot confer tumor protection. In contrast, MDM2-A seems to exhibit a novel transforming potential in cells where p53 function is compromised. These data show that MDM2 splice variants, such as MDM2-A, may provide protection against transformation of normal tissues having intact p53. However, when such splice variants are expressed in tumors that have defects in the p53 pathway, these isoforms may contribute to tumor progression, which could explain why their expression is often associated with aggressive tumor types.

Maternal smoking, alcohol, and coffee use during pregnancy and son's risk of testicular cancer.

It has been suggested that increased risk for testicular cancer occurring worldwide may be due to exposures during fetal development. Lifestyle or environmental exposures may be the most important predictors of risk. However, few studies have directly examined these exposures prospectively. The Child Health and Development Studies is a 40-year follow-up of 20,530 pregnancies occurring between 1959 and 1967. There were 20 cases of testicular cancer diagnosed through 2003 among sons with a maternal interview in early pregnancy. Cases were matched to three controls on birth year and race. Odds ratios and 95% confidence intervals were calculated with exact conditional logistic regression. Compared to controls, mothers of testicular cancer cases were more likely to drink alcohol (unadjusted odds ratio, 3.2; 95% confidence interval, 0.83-15.48 for above vs. below the median for controls) and less likely to drink coffee (unadjusted odds ratio, 0.19; 95% confidence interval, 0.02-1.02 for above vs. below the median). Case mothers were neither more nor less likely to smoke. Although low power may limit interpretation of negative results, the prospective design minimizes bias. In this cohort, maternal serum testosterone in pregnancy was previously reported to be lower in women who drank alcohol. Because populations with high testicular cancer risk also have lower maternal testosterone, we suggest that testosterone could play a role in explaining the higher risk of son's testicular cancer among mothers who drank alcohol during pregnancy.

Polychlorinated biphenyls and risk of testicular germ cell tumors.

Exposure to endocrine-disrupting chemicals, such as polychlorinated biphenyls (PCB), may alter hormonal balance and thereby increase risk of testicular germ cell tumors (TGCT). To study the relationship of PCBs to TGCT, prediagnostic serum samples from 736 cases and 913 controls in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Adjusted odds ratios and 95% confidence intervals were estimated using logistic regression. PCB levels were examined in association with all TGCT and, separately, with each histologic type (seminoma and nonseminoma). Risks associated with seven functional groupings of PCBs, as well as sum of PCBs, were also examined. There were significantly decreased risks of TGCT in association with eight PCBs (PCB-118, PCB-138, PCB-153, PCB-156, PCB-163, PCB-170, PCB-180, and PCB-187) and no association with the remaining three (PCB-99, PCB-101, and PCB-183). The same eight congeners were significantly associated with decreased risk of nonseminoma, whereas five (PCB-138, PCB-153, PCB-156, PCB-163, and PCB-170) were associated with decreased risk of seminoma. All functional groupings of PCBs were also associated with decreased risk of TGCT and of nonseminoma, whereas six of the seven functional groups were associated with decreased risk of seminoma. Sum of PCBs was significantly associated with decreased risk of TGCT (P(trend) = 0.006), nonseminoma (P(trend) = 0.007), and seminoma (P(trend) = 0.05). Overall, these data do not support the hypothesis that PCB exposure increases the risk of TGCT.

Serum organochlorine pesticide residues and risk of testicular germ cell carcinoma: a population-based case-control study.

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.