Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23.

Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined = 6.0 × 10(-9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (PFBAT = 2.3 × 10(-3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.

Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma.

An altered anti-Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV(+) and EBV(-) Hodgkin lymphoma. Among 40 EBV(+) Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti-EBNA-1/anti-EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV(-) Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV(+) disease was significantly associated with a low anti-EBNA-1/anti-EBNA-2 antibody ratio. This distinctive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV(+) but not EBV(-) Hodgkin lymphoma.

Risk of cancer in first- and second-degree relatives of testicular germ cell tumor cases and controls.

Risk factors for testicular germ cell tumors (TGCT) have not been well identified; however, data suggest that risks of cancer in family members of men with TGCT is elevated. Using family history data from 738 cases and 904 controls enrolled in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study from 2002 to 2005, the risk of cancer in first- and second-degree family members of these men was examined. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for reference age of case or control, race/ethnicity of case or control, sex of family member and lineage (maternal vs. paternal). An increased risk of all cancer among first-degree relatives of cases compared to controls was observed (RR = 1.17, 95% CI: 1.01-1.35). There were suggestions of differences in risk when stratifying all relatives by lineage. For maternal relatives, there was a statistically significant increased risk of all cancer (RR = 1.16, 95% CI: 1.04-1.30), digestive tract (RR = 1.52, 95% CI: 1.15-2.00) and male genital organ cancer (RR = 1.70, 95% CI: 1.15-2.51); there was also a suggestion of increased risks of hematopoetic cancers, cancers in the female genital organs and nonmelanoma skin cancer. For paternal relatives, there was a statistically significant association only with decreased risk of lung cancer (RR = 0.69, 95% CI: 0.51-0.94). Thus, this study suggests that there may be aggregation of cancer among families of men diagnosed with TGCT.

Perinatal factors and the risk of testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common cancer among young men in the United States and Western Europe. Prior evidence suggests that TGCT may arise in perinatal life, although few risk factors have yet been identified. To study the etiology of TGCT, the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study enrolled participants and their mothers between 2002 and 2005. Five hundred twenty-seven mothers of cases and 561 mothers of controls provided information on perinatal variables. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95%CI) associated with the candidate risk factors. Analyses were conducted for all TGCT together and for each histologic subgroup (seminoma and nonseminoma) separately. Young maternal age (<20 vs. 20-29 years, OR = 1.51, 95%CI: 1.09-2.10), young paternal age (<25 vs. 25-29 years, OR = 1.45, 95%CI: 1.08-1.94), maternal parity (3 vs. 1, OR = 0.63, 95%CI: 0.44-0.90) and breech birth (OR = 1.92, 95%CI: 1.03-3.56) were associated with risk of TGCT. For seminoma, young maternal age (<20 vs. 20-29 years, OR = 1.67, 95%CI: 1.10-2.54), young paternal age (<25 vs. 25-29 years, OR = 1.53, 95%CI: 1.03-2.27), maternal parity (3 vs. 1, OR = 0.58, 95%CI: 0.35-0.96) and low birth weight (<2,500 g vs. 2,500-4,000 g, OR = 1.82, 95%CI: 1.00-3.30) were risk factors. Nonseminoma was associated with breech birth (OR = 2.44, 95%CI: 1.25-4.78) and Cesarean section (OR = 2.10, 95%CI: 1.25-3.54). These results support the hypothesis that TGCT may originate in very early life.

Insulin-like growth factor 1, insulin-like growth factor-binding protein 3, and testicular germ-cell tumor risk.

Studies have consistently shown that taller men are at increased risk of testicular germ-cell tumors. Thus, it is plausible that factors associated with height may also influence risk of these tumors. The authors examined associations between testicular germ-cell tumor risk and circulating concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) among 517 cases and 790 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study (2002-2005). Odds ratios and 95% confidence intervals were estimated using logistic regression models, adjusting for age, race/ethnicity, height, and body mass index. All tests of significance were two-sided. Overall, there were no associations between IGF-1 or IGFBP-3 concentrations and risk of testicular germ-cell tumors (p > 0.05). However, when cases were separated by histologic type, there was a suggestion of a reduction in seminoma risk associated with the highest concentrations of IGF-1 as compared with the lowest concentrations (odds ratio = 0.66, 95% confidence interval: 0.40, 1.09). Although there were no overall associations with insulin-like growth factor, contrary to expectation, there was a suggestion that IGF-1 concentrations may be inversely associated with risk of seminoma.

Genetic variants in the 8q24 locus and risk of testicular germ cell tumors.

Much evidence supports the premise that population genetic variation contributes significantly to the risk of testicular germ-cell tumor (TGCT). However, investigations of the association between genomic markers and TGCT susceptibility are scarce. Single nucleotide polymorphisms (SNPs) at the locus 8q24 have recently been found to be associated with prostate, colorectal and breast cancer. The US Servicemen's testicular tumor environmental and endocrine determinants (STEED) study was used to investigate the association of 15 specific 8q24 SNPs with TGCT and its two main histologic groups of seminoma and nonseminoma. Conditional and unconditional logistic regression models, adjusted for the matching variables of year of birth, race/ethnicity and serum date, were utilized to produce odds ratios (OR) and 95% confidence intervals (95%CI). The analysis included 680 controls and 568 TGCT cases. In the TGCT analysis, no SNP was associated with risk in both heterozygotes and variant homozygotes. When stratified by histology the seminoma analysis also showed no association with the 8q24 SNPs. Conversely, the analysis of nonseminomas had three tentative associations (rs6470494, OR(genotype AG) = 1.15, 95%CI: 0.86-1.54; OR(genotype GG) = 1.68, 95%CI: 1.04-2.73; p for trend = 0.04) (rs13254738, OR(genotype GT) = 1.04, 95%CI: 0.77-1.40; OR(genotype TT) = 1.62, 95%CI: 1.06-2.49; p for trend = 0.07) (rs10505476, OR(genotype CT) = 0.67, 95%CI: 0.50, 0.91; OR(genotype TT) = 0.81, 95%CI: 0.47-1.39; p for trend = 0.04). There was no linkage disequilibrium between any of the 8q24 SNPs analyzed in this population. In conclusion, this study has found little evidence for an association between the reported 8q24 SNPs and TGCTs, although the findings for nonseminoma may be worth further investigation.

Risk of testicular germ cell tumors and polymorphisms in the insulin-like growth factor genes.

Because taller men are at increased risk of developing testicular germ cell tumors (TGCT), it is conceivable that factors that influence adult height could be related to risk of TGCT. Because common genetic variation in genes of the insulin-like growth factor (IGF) pathway could influence somatic growth, 43 single nucleotide polymorphisms in four IGF genes (IGF-1, IGF-1R, IGF-2, and IGFALS) were genotyped in 577 case and 707 control participants from the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study to assess relationships with TGCT risk; additionally, associations between polymorphisms and adult height were examined. Relationships between polymorphisms and adult height were assessed using adjusted linear regression models, and associations between polymorphisms and TGCT risk were determined by adjusted logistic regression models estimating odds ratios. Although four IGF-1R polymorphisms (rs907806, rs3743258, rs229765, and rs9282714) were associated with height (P trend < 0.05), there were no relationships with any other polymorphism. Overall, there were no associations among polymorphisms or haplotypes in the IGF genes and TGCT risk, with odds ratios ranging from 0.55 to 1.50. Similarly, there was no association among the polymorphisms and risk of specific TGCT histologies (seminoma and nonseminoma). There was a suggestion, however, that adult height may modify the relationship between an IGF-1 haplotype and TGCT risk. These results suggest that, in aggregate, genetic variation in IGF loci is not associated with TGCT risk.

A case-control investigation of immune function gene polymorphisms and risk of testicular germ cell tumors.

There is reason to suspect that testicular germ cell tumor (TGCT) development may be influenced by cytokines, secreted proteins that modulate tumor immune surveillance activity as well as a variety of processes in the testis. To address this hypothesis, we conducted a case-control analysis (508 cases, 608 controls) of 32 putatively functional single-nucleotide polymorphisms (SNP) in 16 immune function genes among non-Hispanic Caucasian participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. The TGFB1 Ex5-73C>T variant was positively associated with TGCT (CT/TT versus CC: odds ratio, 1.73; 95% confidence interval, 1.01-2.95; P(trend) = 0.05); additionally, haplotypes of the assessed TGFB1 SNPs (-509C>T, 327C>T, Ex1-282C>G, and Ex5-73C>T) differed in frequency between cases and controls (all TGCT, P 0.07; seminoma, P 0.04; nonseminoma, P 0.11). We also observed excess frequencies among TGCT cases versus controls of LTA 252G (P(trend) = 0.08) and of the TNF variants -1042C (P(trend) = 0.06), -1036T (P(trend) = 0.07), and -238G (P(trend) = 0.09). Analyses of haplotypes for LTA-TNF SNPs (LTA -91C>A, LTA 252A>G, TNF -863C>A, TNF -857C>T, TNF -308G>A, and -238G>A) were similarly suggestive of an association with TGCT (P = 0.06) and nonseminoma (P = 0.04), but not seminoma (P = 0.21). Polymorphisms in other genes were found to be associated only with seminoma (IL2) or nonseminoma (IFNGR2 and IL10). However, none of the associations remained noteworthy after applying the false discovery rate method to control for multiple testing. In conclusion, our findings suggest that polymorphisms in TGFB1 and LTA/TNF, and possibly other immune function genes, may influence susceptibility to TGCT.

Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

BACKGROUND: Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. METHODS: The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. RESULTS: In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti-double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies. CONCLUSIONS: Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.

Maternal smoking and testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a non-parent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, non-seminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons.

Comparing the population health impacts of medical conditions using routinely collected health care utilization data: nature and sources of variability.

Prevention activities are designed and resourced based on perceptions of the relative population health impacts of various conditions. We examined the nature and variability of rankings of "conditions" based on how they are defined and how their population health impacts are measured. The first listed diagnosis from all hospitalizations and ambulatory visits of U.S. service members during 2002 was used to rank conditions (as defined by two standard classification systems) using five different measures of population health impacts. Less than 10% of all conditions accounted for more than one-half of total population health impact, regardless of how conditions were defined or impacts measured. However, specific conditions with the largest impacts varied depending on the classification system and impact measure. Four groups of related conditions--acute musculoskeletal injuries, pregnancy-related conditions, respiratory infections, and mental disorders (including substance abuse)--accounted for disproportionately large impacts regardless of the measure. The identification of conditions with the largest population health impacts depends on the nature and degree of aggregation in defining conditions and the measure of impact. The findings are relevant to prevention planning and resourcing.

Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis.

CONTEXT: Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. OBJECTIVE: To determine whether antibodies to EBV are elevated before the onset of MS. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n = 83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Serial samples collected before the onset of symptoms were available for 69 matched case-control sets. MAIN OUTCOME MEASURES: Antibodies including IgA against EBV viral capsid antigen (VCA), and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. RESULTS: The average time between blood collection and MS onset was 4 years (range, <1-11 years). The strongest predictors of MS were serum levels of IgG antibodies to EBNA complex or EBNA-1. Among individuals who developed MS, serum antibody titers to EBNA complex were similar to those of controls before the age of 20 years (geometric mean titers: cases = 245, controls = 265), but 2- to 3-fold higher at age 25 years and older (cases = 684, controls = 282; P<.001). The risk of MS increased with these antibody titers; the relative risk (RR) in persons with EBNA complex titers of at least 1280 compared with those with titers less than 80 was 9.4 (95% confidence interval [CI], 2.5-35.4; P for trend <.001). In longitudinal analyses, a 4-fold increase in anti-EBNA complex or anti-EBNA-1 titers during the follow-up was associated with a 3-fold increase in MS risk (EBNA complex: RR , 3.0; 95% CI, 1.3-6.5; EBNA-1: RR, 3.0; 95% CI, 1.2-7.3). No association was found between cytomegalovirus antibodies and MS. CONCLUSION: These results suggest an age-dependent relationship between EBV infection and development of MS.

A Brief Description of the Operation of the DoD Serum Repository.

Beginning in 1985, the United States military has consistently maintained repositories of frozen human serum for force health protection reasons. The separate repositories created by the Army, Navy, and Air Force during the startup of their human immunodeficiency virus (HIV) screening programs were fully combined by 1996, along with the Defense Medical Surveillance System, to form the DoD Serum Repository (DoDSR). Currently comprised of 450,000 square feet of storage space at a constant -30 degrees Celsius, the DoDSR, operated by the Armed Forces Health Surveillance Center (AFHSC), receives approximately 2 million new serum specimens per year as a result of current HIV screening programs and pre- and post-deployment serum collection. Following initial testing for HIV when required, each specimen remains frozen until needed for clinical testing or a public health study, and its physical location is carefully tracked. Certain militarily-relevant research studies occur, though the serum from a specific individual is never allowed to be fully exhausted. AFHSC maintains careful control over the repository, utilizing a scientific review board to determine which requests for serum will be granted. As of 2012, only 0.42% of all of the frozen specimens in the DoDSR had been thawed for any type of use. The addition of new specimen processing capacity and significant changes to policy would be required if more of the specimens were to be used to answer relevant epidemiological, operational, or medical research questions.

Description and utilization of the United States department of defense serum repository: a review of published studies, 1985-2012.

Specimens in the United States Department of Defense (DoD) Serum Repository have accumulated in frozen storage since 1985 when the DoD began universal screening for human immunodeficiency virus. Use of the stored serum for health research has been carefully controlled, but the resulting publications have never been systematically identified or described. The Armed Forces Health Surveillance Center (AFHSC) information systems and open (online) sites were used as data sources. Through 2012, the repository contained 54,542,658 serum specimens, of which 228,610 (0.42%) have been accessed for any purpose. Between 2001 (the first year that comprehensive, digital records were available) and 2012, 65.2% of all approved requests for serum were for healthcare or public health investigations, but greater than 99% of all shipped samples were for research. Using two different methods - a structure search of PubMed and an exhaustive online search based on records from AFHSC - we identified 76 articles published between October 1988 and March 2013 that covered a multitude of infectious diseases, injuries, environmental exposures and mental health conditions through analysis of antibodies, biological metabolic, signaling and regulatory substances, Vitamin D, organochlorines, dioxin, omega-3-fatty acid, and portions of human deoxyribonucleic acid. Despite its operational and scientific value, it appears that the DoD Serum Repository has been underutilized. Changes to policy and increased capacity for specimen processing could increase use of the repository without risking privacy or the availability of specimens for the healthcare of individual service members in the future.

Analysis of adverse events after anthrax immunization in US Army medical personnel.

A broad range of health effects in a cohort of 601 health care personnel, immunized with anthrax vaccine adsorbed (AVA) as a military occupational health requirement, were assessed to evaluate adverse events both qualitatively and quantitatively. Active surveillance showed that localized reactions were common and occurred more often in women than men. Five patients were reported to the Vaccine Adverse Event Reporting System, but only one event could be definitively attributed to immunization, a large localized reaction. Two separate cohort studies, one using nested data from a standardized health risk appraisal instrument and the other comparing rates of outpatient visits and hospitalizations, did not reveal significant differences between AVA-immunized and unimmunized individuals. Our findings suggest that AVA is relatively reactogenic but do not indicate serious adverse health effects due to immunization.

Timing and completeness of routine testing for antibodies to human immunodeficiency virus type 1 among active duty members of the U.S. Armed Forces.

Since 1985, the U.S. Armed Forces have conducted routine testing of personnel for antibodies to human immunodeficiency virus type 1. Sera that remain after testing are archived in the Department of Defense serum repository for potential uses in medical surveillance, clinical, and research activities. The goal of this study was to document the timing and completeness of routine human immunodeficiency virus type 1 testing among active duty military personnel and to identify factors associated with more recent testing. Demographic characteristics for active duty personnel were obtained from the Defense Medical Surveillance System. Of all individuals on active duty on August 31, 2001 (N = 1,370,367), 98.6% had been tested. Older personnel, those with postgraduate degrees, and married personnel had the longest time intervals since their most recent tests. The results of this analysis may inform the planning and conduct of human immunodeficiency virus type 1 prevention programs as well as deployment-related or other surveillance activities.

Genetic contributions to the association between adult height and testicular germ cell tumors.

BACKGROUND: Previously, we have shown that increasing adult height is associated with increased risk of testicular germ-cell tumor (TGCT). Recently, a number of single nucleotide polymorphisms (SNPs) have been found to be related to height. We examined whether these SNPs were associated with TGCT and whether they explained the relationship between height and TGCT. METHODS: We genotyped 15 height-related SNPs in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study. DNA was extracted from buccal cell samples and Taqman assays were used to type the selected SNPs. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: There were 561 cases and 676 controls for analysis. Two SNPs were found to be associated with risk of TGCT, rs6060373 (CC vs TT, OR = 1.51, 95% CI: 1.06-2.15) and rs143384 (CC vs TT, OR = 1.53, 95% CI: 1.09-2.15). rs6060373 is an intronic polymorphism of ubiquinol-cytochrome c reductase complex chaperone (UQCC), and rs143384 is a 5'UTR polymorphism of growth differentiation factor 5 (GDF5). No individual SNP attenuated the association between height and TGCT. Adjustment for all SNPs previously associated with adult height reduced the associations between adult height and TGCT by ~8.5%, although the P-value indicated only weak evidence that this difference was important (P = 0.26). CONCLUSIONS: This novel analysis provides tentative evidence that SNPs which are associated with adult height may also share an association with risk of TGCT.

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 IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel.

The seroconversion rates and geometric mean concentrations (GMC) of IgG anti-PA for stored sera from U.S. military personnel immunized 3, 4, and 6 times with the U.S. licensed anthrax vaccine adsorbed were studied. Anti-PA IgG concentrations were measured by ELISA. All 246 vaccinees had low but detectable pre-immunization anti-PA IgG (GMC 1.83 microg/mL). Three doses elicited a GMC of 59.92 microg/mL and a seroconversion rate of 85.3%, four doses elicited a GMC of 157.44 microg/mL and 67.9% and the sixth of 276.95 microg/mL and 45.5%, respectively. The forth dose elicited 100% seroconversion compared to the pre-immunization level. These results should facilitate comparison between different immunization schedules and new vaccines.