Association of juvenile idiopathic arthritis with maternal infection: a case control study.

OBJECTIVE: Maternal infection has been posited as a risk factor for childhood autoimmune disease such as type I diabetes. Given that similar studies in JIA are scant, our objective was to evaluate the association between Juvenile Idiopathic Arthritis (JIA) and maternal infection. METHODS: This case-control study used an existing database that included 1290 JIA cases and 6072 controls matched on birth year. Maternal infection information was obtained from Washington State birth records. JIA diagnosis and categories were confirmed through chart review. Logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: JIA was not associated with maternal infection (OR = 1.02, 95%CI: 0.8-1.3). There was no association between JIA and maternal infection for persistent oligoarticular, RF negative polyarticular, or enthesitis-related JIA. There was suggestive evidence of an increased association of maternal infection with JIA in females in sex-stratified analysis. CONCLUSIONS: We did not observe an increased risk of JIA in children exposed to maternal infection. Suggestive evidence of differential sex-specific results warrants further study.

Association of prenatal exposure to ambient air pollution with adverse birth outcomes and effect modification by socioeconomic factors.

BACKGROUND: Maternal exposure to air pollution has been associated with birth outcomes; however, few studies examined biologically critical exposure windows shorter than trimesters or potential effect modifiers. OBJECTIVES: To examine associations of prenatal fine particulate matter (PM2.5), by trimester and in biologically critical windows, with birth outcomes and assess potential effect modifiers. METHODS: This study used two pregnancy cohorts (CANDLE and TIDES; N = 2099) in the ECHO PATHWAYS Consortium. PM2.5 was estimated at the maternal residence using a fine-scale spatiotemporal model, averaged over pregnancy, trimesters, and critical windows (0-2 weeks, 10-12 weeks, and last month of pregnancy). Outcomes were preterm birth (PTB, <37 completed weeks of gestation), small-for-gestational-age (SGA), and continuous birthweight. We fit multivariable adjusted linear regression models for birthweight and Poisson regression models (relative risk, RR) for PTB and SGA. Effect modification by socioeconomic factors (maternal education, household income, neighborhood deprivation) and infant sex were examined using interaction terms. RESULTS: Overall, 9% of births were PTB, 10.4% were SGA, and mean term birthweight was 3268 g (SD = 558.6). There was no association of PM2.5 concentration with PTB or SGA. Lower birthweight was associated with higher PM2.5 averaged over pregnancy (ß -114.2, 95%CI -183.2, -45.3), during second (ß -52.9, 95%CI -94.7, -11.2) and third (ß -45.5, 95%CI -85.9, -5.0) trimesters, and the month prior to delivery (ß -30.5, 95%CI -57.6, -3.3). Associations of PM2.5 with likelihood of SGA and lower birthweight were stronger among male infants (p-interaction ≤0.05) and in those with lower household income (p-interaction = 0.09). CONCLUSIONS: Findings from this multi city U.S. birth cohort study support previous reports of inverse associations of birthweight with higher PM2.5 exposure during pregnancy. Findings also suggest possible modification of this association by infant sex and household income.

Residential proximity to major roads and fecundability in a preconception cohort.

Emerging evidence from animal and human studies indicates that exposure to traffic-related air pollution may adversely affect fertility. METHODS: Among 7,342 female pregnancy planners from the United States and 1,448 from Canada, we examined the association between residential proximity to major roads and fecundability, the per-cycle probability of conception. From 2013 to 2019, women 21-45 years old who were trying to conceive without fertility treatment completed an online baseline questionnaire and follow-up questionnaires every 8 weeks for up to 12 months or until pregnancy. We geocoded residential addresses reported at baseline and during follow-up, and calculated distance to nearest major roads and length of major roads within buffers of 50, 100, 300, and 400 meters around the residence as proxies for traffic-related air pollution. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for individual- and neighborhood-level characteristics. RESULTS: In the United States, the FR comparing women who lived <50 meters with those who lived ≥400 meters from the closest major road was 0.88 (95% CI = 0.80, 0.98). The association among Canadian women was similar in magnitude, but less precise (FR = 0.93; 95% CI = 0.74, 1.16). Likewise, length of major roads within buffers of 50 and 100 meters was associated with lower fecundability in both countries; associations were attenuated within larger buffers. CONCLUSIONS: These results are consistent with the hypothesis that traffic-related air pollution or other near-road exposures may adversely affect fecundability.

Ambient Air Pollution Exposure and Fecundability in Women Undergoing In Vitro Fertilization.

BACKGROUND: Limited research suggests ambient air pollution impairs fecundity but groups most susceptible have not been identified. We studied whether long-term ambient air pollution exposure prior to an in vitro fertilization (IVF) cycle was associated with successful livebirth, and whether associations were modified by underlying infertility diagnosis. METHODS: Data on women initiating their 1st autologous IVF cycle in 2012-13 were obtained from four U.S. clinics. Outcomes included pregnancy, pregnancy loss, and livebirth. Annual average exposure to fine particulate matter (PM2.5), PM10, and nitrogen dioxide (NO2) prior to IVF start were estimated at residential address using a validated national spatial model incorporating land-use regression and universal kriging. We also assessed residential distance to major roadway. We calculated risk ratios (RR) using modified Poisson regression and evaluated effect modification (EM) by infertility diagnosis on additive and multiplicative scales. RESULTS: Among 7,463 eligible participants, 36% had a livebirth. There was a non-significant indication of an association between PM2.5 or NO2 and decreased livebirth and increased pregnancy loss. Near roadway residence was associated with decreased livebirth (RR: 0.96, 95% CI: 0.82, 0.99. There was evidence for EM between high exposure to air pollutants and a diagnosis of diminished ovarian reserve (DOR) or male infertility and decreased livebirth. CONCLUSIONS: Despite suggestive but uncertain findings for the overall effect of air pollution on fecundity, we found a suggestive indication that there may be synergistic effects of air pollution and DOR or male infertility diagnosis on livebirth. This suggests two possible targets for future research and intervention.

Urinary cadmium and estimated dietary cadmium in the Women's Health Initiative.

Cadmium, a heavy metal dispersed in the environment as a result of industrial and agricultural applications, has been implicated in several human diseases including renal disease, cancers, and compromised bone health. In the general population, the predominant sources of cadmium exposure are tobacco and diet. Urinary cadmium (uCd) reflects long-term exposure and has been frequently used to assess cadmium exposure in epidemiological studies; estimated dietary intake of cadmium (dCd) has also been used in several studies. The validity of dCd in comparison with uCd is unclear. This study aimed to compare dCd, estimated from food frequency questionnaires, to uCd measured in spot urine samples from 1,002 participants of the Women's Health Initiative. Using linear regression, we found that dCd was not statistically significantly associated with uCd (ß=0.006, P-value=0.14). When stratified by smoking status, dCd was not significantly associated with uCd both in never smokers (ß=0.006, P-value=0.09) and in ever smokers (ß=0.003, P-value=0.67). Our results suggest that because of the lack of association between estimated dCd and measured uCd, dietary estimation of cadmium exposure should be used with caution in epidemiologic studies.

High prevalence of screen detected prostate cancer in West Africans: implications for racial disparity of prostate cancer.

PURPOSE: To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana. MATERIALS AND METHODS: We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies. RESULTS: Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml. CONCLUSIONS: In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology.

Dietary cadmium exposure and risk of breast, endometrial, and ovarian cancer in the Women's Health Initiative.

BACKGROUND: In vitro and animal data suggest that cadmium, a heavy metal that contaminates some foods and tobacco plants, is an estrogenic endocrine disruptor. Elevated estrogen exposure is associated with breast, endometrial, and ovarian cancer risk. OBJECTIVES: We examined the association between dietary cadmium intake and risk of these cancers in the large, well-characterized Women's Health Initiative (WHI). METHODS: A total of 155,069 postmenopausal women, 50-79 years of age, who were enrolled in the WHI clinical trials or observational study, participated in this study. We estimated dietary cadmium consumption by combining baseline food frequency questionnaire responses with U.S. Food and Drug Administration data on food cadmium content. Participants reported incident invasive breast, endometrial, or ovarian cancer, and WHI centrally adjudicated all cases through August 2009. We applied Cox regression to estimate adjusted hazard ratios (HRs) and 95% CIs for each cancer, comparing quintiles of energy-adjusted dietary cadmium intake. RESULTS: Over an average of 10.5 years, 6,658 invasive breast cancers, 1,198 endometrial cancers, and 735 ovarian cancers were reported. We observed no statistically significant associations between dietary cadmium and risk of any of these cancers after adjustment for potential confounders including total dietary energy intake. Results did not differ in any subgroup of women examined. CONCLUSIONS: We found little evidence that dietary cadmium is a risk factor for breast, endometrial, or ovarian cancers in postmenopausal women. Misclassification in dietary cadmium assessment may have attenuated observed associations.

The association between inflammation-related genes and serum androgen levels in men: the prostate, lung, colorectal, and ovarian study.

BACKGROUND: Androgens and inflammation have been implicated in the etiology of several cancers, including prostate cancer. Serum androgens have been shown to correlate with markers of inflammation and expression of inflammation-related genes. METHODS: In this report, we evaluated associations between 9,932 single nucleotide polymorphisms (SNPs) marking common genetic variants in 774 inflammation-related genes and four serum androgen levels (total testosterone [T], bioavailable T [BioT]; 5α-androstane-3α, 17ß-diol glucuronide [3αdiol G], and 4-androstene-3,17-dione [androstenedione]), in 560 healthy men (median age 64 years) drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Baseline serum androgens were measured by radioimmunoassay. Genotypes were determined as part of the Cancer Genetic Markers of Susceptibility Study genome-wide scan. SNP-hormone associations were evaluated using linear regression of hormones adjusted for age. Gene-based P values were generated using an adaptive rank truncated product (ARTP) method. RESULTS: Suggestive associations were observed for two inflammation-related genes and circulating androgen levels (false discovery rate [FDR] q-value <0.1) in both SNP and gene-based tests. Specifically, T was associated with common variants in MMP2 and CD14, with the most significant SNPs being rs893226G > T in MMP2 and rs3822356T > C in CD14 (FDR q-value = 0.09 for both SNPs). Other genes implicated in either SNP or gene-based tests were IK with T and BioT, PRG2 with T, and TNFSF9 with androstenedione. CONCLUSION: These results suggest possible cross-talk between androgen levels and inflammation pathways, but larger studies are needed to confirm these findings and to further clarify the interrelationship between inflammation and androgens and their effects on cancer risk.

Prostate cancer incidence rates in Africa.

African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973-2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7-38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7-19.8). These rates were considerably lower than those of 80.0-195.3 observed among African Americans. Rates in Africa increased over time (1987-2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa.

Chronic typhoid infection and the risk of biliary tract cancer and stones in Shanghai, China.

Previous studies have shown a positive association between chronic typhoid carriage and biliary cancers. We compared serum Salmonella enterica serovar Typhi antibody titers between biliary tract cancer cases, biliary stone cases without evidence of cancer, and healthy subjects in a large population-based case-control study in Shanghai, China.Participants included 627 newly diagnosed primary biliary tract cancer patients; 1,037 biliary stone cases (774 gallbladder and 263 bile-duct) and 959 healthy subjects without a history of cancer, randomly selected from the Shanghai Resident Registry.Overall only 6/2,293 (0.26%) were Typhi positive. The prevalence of Typhi was 1/457 (0.22%), 4/977 (0.41%), and 1/859 (0.12%) among cancer cases, biliary-stone cases, and population controls, respectively.We did not find an association between Typhi and biliary cancer in Shanghai, due to the very low prevalence of chronic carriers in this population.The low seroprevalence of S. Typhi in Shanghai is unlikely to explain the high incidence of biliary cancers in this population.

Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.

BACKGROUND: Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder. METHODS: To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels. RESULTS: Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05). CONCLUSIONS: These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels. IMPACT: These results might provide some clues for the strong link between 8q24 and prostate cancer risk.

International trends in the incidence of testicular cancer, 1973-2002.

BACKGROUND: Whereas testicular cancer incidence rates have been widely reported in populations of Northern European ancestry, rates in other populations have been less frequently examined. In a prior report, global testicular cancer incidence rates and trends for the years 1973 to 1997 were summarized. The current report extends these analyses with an additional 5 years of data from Cancer Incidence in Five Continents. METHODS: Age-standardized incidence rates over successive 5-year time periods were obtained for populations in the Americas, Asia, Europe, and Oceania. RESULTS: In general, testicular cancer incidence remained highest in Northern European populations (8.0-9.0 per 100,000) and lowest in Asian and African populations (<1 per 100,000). One notable exception to this pattern, however, was the very high rate reported by the Valdivia, Chile registry (8.8 per 100,000). In many populations, rates rose between 1973 and 2002, although the increases were strongest and most consistent among populations of European ancestry. In certain European populations, such as those of Denmark and of Geneva, Switzerland, some recent plateauing of rates was evident. There was little evidence of increase and possible evidence of a modest decline in rates among east Asian populations. Trends by histology (seminoma and nonseminoma) were generally similar to one another. CONCLUSIONS: Risk of testicular cancer remains relatively high in Northern European populations and low in Asian and African populations. Similar trends by histology suggest common risk factors. EFFECT: Reasons for increasing rates among Northern Europeans and stable or declining rates among East Asians are unexplained, supporting the need for future etiologic studies.

Measuring serum melatonin in epidemiologic studies.

BACKGROUND: Epidemiologic data on serum melatonin, a marker of circadian rhythms, and cancer are sparse due largely to the lack of reliable assays with high sensitivity to detect relatively low melatonin levels in serum collected during daylight, as commonly available in most epidemiologic studies. METHODS: To help expand epidemiologic research on melatonin, we assessed the reproducibility and refined a currently available melatonin RIA, and evaluated its application to epidemiologic investigations by characterizing melatonin levels in serum, urine, and/or plasma in 135 men from several ethnic groups. RESULTS: Reproducibility was high for the standard 1.0-mL serum [mean coefficient of variation (CV), 6.9%; intraclass correlation coefficient (ICC), 97.4%; n = 2 serum pools in triplicate] and urine-based (mean CV, 3.5%; ICC, 99.9%) assays. Reproducibility for the 0.5-mL refined-serum assay was equally good (mean CV, 6.6%; ICC, 99.0%). There was a positive correlation between morning serum melatonin and 6-sulfatoxymelatonin in 24-hour urine (r = 0.46; P = 0.008; n = 49 subjects). Melatonin levels in serum-plasma pairs had a high correlation (r = 0.97; P < 1x10(-4); n = 20 pairs). Morning serum melatonin levels were five times higher than those from the afternoon (before 9 a.m. mean, 11.0 pg/mL, versus after 11 a.m. mean, 2.0 pg/mL). Chinese men had lower melatonin levels (mean, 3.4 pg/mL), whereas Caucasian, African-American, and Ghanaian men had similar levels (mean, 6.7-8.6 pg/mL). CONCLUSIONS: These results suggest that melatonin can be detected reliably in serum samples collected in epidemiologic studies in various racial groups. IMPACT: With improved assays, it may be possible to investigate the role of melatonin and the emerging circadian rhythm hypothesis in cancer etiology in epidemiologic studies.

Sex disparities in cancer incidence by period and age.

BACKGROUND: Cancer epidemiology articles often point out that cancer rates tend to be higher among males than females yet rarely is this theme the subject of investigation. METHODS: We used the Surveillance, Epidemiology and End Results program data to compute age-adjusted (2000 U.S. standard population) sex-specific incidence rates and male-to-female incidence rate ratios (IRR) for specific cancer sites and histologies for the period 1975 to 2004. RESULTS: The 10 cancers with the largest male-to-female IRR were Kaposi sarcoma (28.73), lip (7.16), larynx (5.17), mesothelioma (4.88), hypopharynx (4.13), urinary bladder (3.92), esophagus (3.49), tonsil (3.07), oropharynx (3.06), and other urinary organs (2.92). Only 5 cancers had a higher incidence in females compared with males: breast (0.01), peritoneum, omentum, and mesentery (0.18), thyroid (0.39), gallbladder (0.57), and anus, anal canal, and anorectum (0.81). Between 1975 and 2004, the largest consistent increases in male-to-female IRR were for cancers of the tonsil, oropharynx, skin excluding basal and squamous, and esophagus, whereas the largest consistent decreases in IRR were for cancers of the lip and lung and bronchus. Male-to-female IRRs varied considerably by age, the largest increases of which were for ages 40 to 59 years for tonsil cancer and hepatocellular carcinoma. The largest decreases in male-to-female IRR by age, meanwhile, were for ages 30 to 49 years for thyroid cancer, ages >70 years for esophageal squamous cell carcinoma, and ages >30 years for lung and bronchus cancer. CONCLUSION: These observations emphasize the importance of sex in cancer etiopathogenesis and may suggest novel avenues of investigation.

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.

Persistent organochlorine pesticides and risk of testicular germ cell tumors.

BACKGROUND: Exposure to endocrine-disrupting chemicals, such as persistent organochlorine pesticides, has been suggested to increase the risk of testicular germ cell tumors (TGCTs). METHODS: To study the relationship of POP exposure to TGCT risk, prediagnostic serum samples from 754 case subjects and 928 control subjects enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study were analyzed for cis-nonachlor, trans-nonachlor, oxychlordane, total chlordanes, beta-hexachlorocyclohexane, mirex, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), and p,p'-dichlorodiphenyltrichloroethane. Adjusted odds ratios (ORs) and their associated 95% confidence intervals (CIs) for the risk of TGCT overall and for the histological subgroups, seminoma and nonseminoma, were estimated using multivariable logistic regression. All statistical tests were two-sided. RESULTS: TGCT risk was statistically significantly associated with higher plasma levels of p,p'-DDE (for highest quartile [Q4] vs lowest quartile [Q1], OR = 1.71, 95% CI = 1.23 to 2.38, P(trend) = .0002) and of two chlordane components, cis-nonachlor (Q4 vs Q1, OR = 1.56, 95% CI = 1.11 to 2.18, P(trend) = .009) and trans-nonachlor (Q4 vs Q1, OR = 1.46, 95% CI = 1.07 to 2.00, P(trend) = .026). Seminoma risk was statistically significantly associated with p,p'-DDE (Q4 vs Q1, OR = 1.91, 95% CI = 1.22 to 2.99, P(trend) = .0008), cis-nonachlor (Q4 vs Q1, OR = 1.93, 95% CI = 1.27 to 2.93, P(trend) = .0045), trans-nonachlor (Q4 vs Q1, OR = 1.72, 95% CI = 1.11 to 2.67, P(trend) = .033), and a chlordane metabolite, oxychlordane (Q4 vs Q1, OR = 1.64, 95% CI = 1.04 to 2.60, P(trend) = .048), whereas nonseminoma risk showed a statistically significant association with p,p'-DDE only (Q4 vs Q1, OR = 1.63, 95% CI = 1.10 to 2.42, P(trend) = .0044). CONCLUSIONS: Increased exposure to p,p'-DDE may be associated with the risk of both seminomatous and nonseminomatous TGCTs, whereas exposure to chlordane compounds and metabolites may be associated with the risk of seminoma. Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these persistent organic pesticides during fetal life or via breast feeding may increase the risk of TGCT in young men.

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.

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.