High prevalence of non-alcoholic fatty liver disease and metabolic risk factors in Guatemala: A population-based study.

BACKGROUND: There are no data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in general population samples in Guatemala or in other Central American countries. The prevalence and distribution of NAFLD and its associated risk factors were evaluated in a population-based sample of adults in Guatemala. METHODS: Cross-sectional study of 411 men and women 40 years of age or older residing in urban and rural areas of Guatemala. Metabolic outcomes included obesity, central obesity, hypercholesterolemia, diabetes, and metabolic syndrome (MetS). Liver disease outcomes included elevated liver enzymes, elevated Fatty Liver Index (FLI), and elevated FIB-4 score. RESULTS: The overall prevalence of obesity, central obesity, diabetes, and MetS were 30.9, 74.3, 21.6, and 64.2%, respectively. The fully-adjusted prevalence ratios (95% CI) for obesity, central obesity, diabetes, and MetS comparing women to men were 2.83 (1.86-4.30), 1.72 (1.46-2.02), 1.18 (1.03-1.34), and 1.87 (1.53-2.29), respectively. The overall prevalence of elevated liver enzymes (ALT or AST), elevated FLI, and elevated FIB-4 scores were 38.4, 60.1, and 4.1%, respectively. The fully-adjusted prevalence ratios (95% CI) for elevated liver enzymes (either ALT or AST) and elevated FLI score comparing women to men were 2.99 (1.84-4.86) and 1.47 (1.18-1.84), respectively. CONCLUSIONS: The prevalence of metabolic abnormalities and liver outcomes in this general population study was very high. The prevalence of metabolic and liver abnormalities was particularly high among women, an observation that could explain the atypical 1:1 male to female ratio of liver cancer in Guatemala.

Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. METHODS: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). RESULTS: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. CONCLUSIONS: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes.

BACKGROUND: Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication. METHODS: To address this association, we conducted a nested case-control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. RESULTS: In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45-1.20) for metformin-only, 1.10 (95% CI=0.66-1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58-1.37) for metformin+other OH, 1.11 (95% CI=0.60-2.05) for metformin+insulin, 0.81 (95% CI=0.23-2.85) for other OH+insulin, and 0.72 (95% CI=0.18-2.84) for insulin-only). Stratification by duration of diabetes did not alter the results. CONCLUSIONS: Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.

Association of serum α-tocopherol, ß-carotene, and retinol with liver cancer incidence and chronic liver disease mortality.

BACKGROUND: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, ß-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. METHODS: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. RESULTS: Higher ß-carotene and retinol levels were associated with less liver cancer (ß-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (ß-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of ß-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. CONCLUSIONS: Our findings suggest that higher concentrations of ß-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.

Effects of α-tocopherol and ß-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

BACKGROUND: Recent data suggest the possible benefits of α-tocopherol and ß-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. METHODS: We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) ß-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes. RESULTS: Supplemental α-tocopherol, ß-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. CONCLUSIONS: Long-term supplemental α-tocopherol or ß-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

BACKGROUND: Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. METHODS: We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. RESULTS: Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. CONCLUSION: These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Childhood infections, orchitis and testicular germ cell tumours: a report from the STEED study and a meta-analysis of existing data.

BACKGROUND: Similarities between the age-specific incidence pattern of testicular germ cell tumours (TGCTs) and the age-specific incidence pattern of cancers of viral origin prompted us to evaluate the relationship between common infections occurring during childhood or young adult life and TGCT using existing data from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study. METHODS: TGCT cases diagnosed between 2002 and 2005 (n=767) were matched on age, race and serum draw date to at least one control (n=929). RESULTS: None of the infections evaluated were associated with TGCT risk. Further, a meta-analysis of mumps and mumps orchitis or orchitis infection did not support an association with TGCT (mumps pooled odds ratio (OR): 1.03, 95% confidence interval (CI): 0.89-1.20; mumps orchitis or orchitis pooled OR: 1.80, 95% CI: 0.74-4.42). CONCLUSION: Based on our evaluation of childhood and early life infections and meta-analyses of mumps and mumps orchitis and/or orchitis, TGCT does not appear to be associated with common childhood infections.

Risk of liver cancer among US male veterans with cirrhosis, 1969-1996.

BACKGROUND: Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected. METHODS: Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate. RESULTS: Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR=37.59, 95% CI: 22.57-62.61), lowest among men with alcohol-related cirrhosis (HR=8.20, 95% CI: 7.55-8.91) and intermediate among men with idiopathic cirrhosis (HR=10.45, 95% CI: 8.52-12.81), when compared with those without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40-9.33) in 1969-1973 to 34.71 (95% CI: 23.10-52.16) in 1992-1996 for those with cirrhosis compared with those without. CONCLUSION: In conclusion, the significantly increased HR of developing liver cancer among men with cirrhosis compared with men without cirrhosis in the United States may be contributing to the increasing incidence of liver cancer.

Trends in sex hormone concentrations in US males: 1988-1991 to 1999-2004.

Previous studies suggest that male testosterone concentrations have declined over time. To explore this in a large US population, we examined testosterone and free testosterone concentrations in National Health and Nutrition Examination Surveys (NHANES) from 1988-1991 and 1999-2004. We also examined sex hormone-binding globulin (SHBG), estradiol, and androstanediol glucuronide (3α-diol-G) over the same period. Non-Hispanic white, non-Hispanic black, and Mexican-American men from 1988-1991 and 1999-2004 NHANES surveys who were ≥20 years old and had serum from morning blood draws were included in this analysis (1988-1991: N = 1,413; 1999-2004: N = 902). Testosterone, estradiol and SHBG were measured by competitive electrochemiluminescence immunoassays and 3α-diol-G was measured by enzyme immunoassay. Free testosterone was calculated using testosterone and SHBG values. Adjusted mean hormone concentrations were estimated using linear regression, accounting for NHANES sampling weights and design, age, race/ethnicity, body mass index, waist circumference, alcohol use and smoking. Differences in adjusted mean concentrations (Δ) and two-sided p-values were calculated; p < 0.05 was statistically significant. Overall, 3α-diol-G and estradiol declined between 1988-1991 and 1999-2004, but there was little change in testosterone, free testosterone, or SHBG (Δ: 3α-diol-G = -1.83 ng/mL, p < 0.01; estradiol = -6.07 pg/mL, p < 0.01; testosterone = -0.03 ng/mL, p = 0.75; free testosterone = -0.001 ng/mL, p = 0.67; SHBG = -1.17 nmol/L, p = 0.19). Stratification by age and race revealed that SHBG and 3α-diol-G declined among whites 20-44 years old (Δ: SHBG = -5.14 nmol/L, p < 0.01; 3α-diol-G = -2.89 ng/mL, p < 0.01) and free testosterone increased among blacks 20-44 years old (Δ: 0.014 ng/mL, p = 0.03). Estradiol declined among all ages of whites and Mexican-Americans. In conclusion, there was no evidence for testosterone decline between 1988-1991 and 1999-2004 in the US general population. Subgroup analyses suggest that SHBG and 3α-diol-G declined in young white men, estradiol declined in white and Mexican-American men, and free testosterone increased in young black men. These changes may be related to the increasing prevalence of reproductive disorders in young men.

Gonadal and extragonadal germ cell tumours in the United States, 1973-2007.

Germ cell tumours (GCTs) most often arise in the gonads, but some develop extragonadally. The aim of this study was to examine gender- and race-specific trends in incidence and survival of gonadal (GGCTs) and extragonadal GCTs (EGCTs) in the US from 1973 to 2007. We also examined the topographical distribution of EGCTs by race and gender. We estimated age-specific and age-standardized incidence rates and 5-year relative survival rates (RSR) of GCTs using the Surveillance, Epidemiology and End Results (SEER) Program (SEER nine registries). GCTs and their topographical sites were identified using ICD-O morphology and topography codes. Of 21,170 GCTs among males, 5.7% were extragonadal (Whites 5.5%; Blacks 16.3%). Of 2093 GCTs among females, 39.3% were extragonadal (Whites, 36.9%; Blacks 51.0%). The incidence of GGCT was much higher among White (56.3/1,000,000) than Black males (10.0/1,000,000), while there was no difference in incidence between White and Black females (3.2/1,000,000). The rates of EGCT among men and women of both races were similar (range:1.9-3.4/1,000,000). The most frequent extragonadal sites were mediastinum among males and placenta among females. The 5-year RSR of testicular GCT was higher among Whites (97%) than Blacks (90%), as was the 5-year RSR of ovarian GCT (Whites, 92%; Blacks 85%). In general, the 5-year RSRs of EGCTs were lower than the 5-year RSRs of GGCTs. The different incidence trends of GGCTs and EGCTs and distinct age-specific incidence patterns by anatomical site of EGCTs suggest that GGCTs and EGCTs may have different aetiologies.

Organochlorine compounds and testicular dysgenesis syndrome: human data.

Cryptorchidism, hypospadias, subfertility and testicular germ-cell tumour have been suggested to comprise a testicular dysgenesis syndrome (TDS) based on the premise that each may derive from perturbations of embryonal programming and gonadal development during foetal life. Endocrine-disrupting chemicals have been hypothesized to be associated with these disorders, given the importance of sex steroid hormones in urogenital development and homeostasis. Organochlorines are one such set of compounds which are defined as containing between one and ten covalently bonded chlorine atoms. These compounds are persistent pollutants with long half-lives, accumulate in adipose tissue when ingested, bioaccumulate and biomagnify, and have complex and variable toxicological profiles. Examples of organochlorines include dichloro-diphenyl-trichloroethane and its metabolites, polychlorinated biphenyls, and chlordane. In this comprehensive review of human epidemiologic studies which have tested for associations between organochlorines and facets of TDS, we find evidence for associations between the exposures p,p'-DDE, cis-nonachlor and trans-nonachlor with testicular germ-cell tumour. The sum of the evidence from human epidemiological studies does not indicate any association between specific organochlorines studied and cryptorchidism, hypospadias or fertility. Many other endocrine-disrupting chemicals, including additional organochlorines, have yet to be assessed in relation to disorders associated with TDS, yet study of such chemicals has strong scientific merit given the relevance of such hypotheses to urogenital development.

Impact of classification of mixed germ-cell tumours on incidence trends of non-seminoma.

Seminomas and non-seminomas [embryonal carcinomas, yolk sac tumours, teratomas, choriocarcinomas, mixed germ-cell tumours (MGCT)] are the major histological types of testicular germ-cell tumours (TGCT). TGCTs composed of both seminomatous and non-seminomatous elements have been coded as their non-seminoma component in the World Health Organization classification. In the late 1980s, a provisional International Classification of Diseases for Oncology (ICD-O) morphology code for MGCT was introduced. Using data from the Surveillance, Epidemiology and End Results Program and two population-based German cancer registries, we examined the impact of MGCT classification on TGCT trends. Cases were identified using ICD-O topography (ICD-9: 186; ICD-10: C62) and morphology codes (seminoma=9060-9062, 9064; embryonal carcinoma=9070; yolk sack tumour=9071; teratoma=9080-9084, 9102; choriocarcinoma=9100, 9101; MGCT=9085; all non-seminoma=9065-9102). As MGCTs and teratoma are often grouped as a single histological group, we analysed teratoma both including and excluding MGCTs. Between 1988 and 2007, incidence rates of MGCT in the US increased 407%. Rates of teratoma including MGCT increased 80%, whereas rates of teratoma excluding MGCT decreased 71%. Rates of embryonal carcinoma [-40%] and choriocarcinoma [-22%] also declined, suggesting that the code for MGCT is now being used for any mixed histology. Similar declines in incidence were observed in the German comparison populations. The declines in incidence of teratoma (excluding MGCT), embryonal carcinoma and choriocarcinoma in the US data since 1988 are likely in part because of increases in classifying any TGCT with mixed histology as MGCT. These results suggest that analysis of trends in specific histological types of non-seminoma should be interpreted cautiously.

Baldness, acne and testicular germ cell tumours.

Androgen levels during critical periods of testicular development may be involved in the aetiology of testicular germ cell tumours (TGCT). We evaluated the roles of adolescent and early adult life correlates of androgen exposure and TGCT in a hospital-based case-control study. TGCT cases (n=187) and controls (n=148), matched on age, race and state of residence, participated in the study. Unconditional logistic regression was used to estimate associations between TGCT and male pattern baldness, severe acne, markers of puberty onset and body size. Cases were significantly less likely to report hair loss than controls [odds ratio (OR): 0.6; 95% confidence interval (CI): 0.4, 1.0]. Amount of hair loss, increasing age at onset and increasing rate of loss were all inversely associated with TGCT (rate of hair loss: p-trend=0.03; age at onset: p-trend=0.03; amount of hair loss: p-trend=0.01). History of severe acne was inversely associated with TGCT (OR: 0.5; 95% CI: 0.3, 0.9) and height was positively associated with TGCT (p-trend=0.02). Increased endogenous androgen levels during puberty and early adulthood may be associated with a decreased risk of TGCT. Additional studies of endogenous hormone levels during puberty and early adult life are warranted, especially studies evaluating the role of androgen synthesis, metabolism and uptake.

A systematic review and meta-analysis of the relationship between body size and testicular cancer.

BACKGROUND: Studies assessing the relationships of anthropometry and testicular germ-cell tumour (TGCT) have reported heterogeneous findings. METHODS: We undertook a systematic review and meta-analysis of the associations between adult height, weight, body mass index (BMI), and testicular cancer. Search strategies were conducted in PubMed, EMBASE, Scopus, and Web of Science on 26 May 2009. Studies that met our inclusion criteria were included in meta-analytic models using STATA 11. RESULTS: A total of 3255 references were retrieved, of which 14 met the inclusion criteria. Random effects meta-analysis found adult height (odds ratio (OR) per 5-cm increase 1.13, 95% confidence interval (CI) 1.07-1.19, P<0.001) and weight (OR overweight vs normal 0.92, 95% CI 0.86-0.98, P=0.011) to be associated with TGCT. The meta-analysis of weight and TGCT produced a summary estimate, which indicated no association, although an analysis restricted studies to North American was suggestive of association (OR per 1-kg increase 1.01, 95% CI 1.00-1.01, P<0.001). CONCLUSIONS: This systematic review and meta-analysis has found evidence for a positive association of adult height and TGCT, and tentative evidence for an inverse association of BMI and TGCT.

Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone-metabolizing genes.

It has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p'-dichlorodiphenyldichloroethylene, chlordane-related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01-3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p-interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45-55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions < 0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.

Cross-sectional associations between healthy eating index and sex steroid hormones in men-National Health and Nutrition Examination Survey 1999-2002.

BACKGROUND: Diet plays an important role in health and is a modifiable risk factor for chronic diseases. In men, sex steroid hormones influence, and are influenced by, a number of health states. Specific dietary patterns have been found to alter sex steroid hormone levels in observational and intervention studies. Thus, we hypothesized that dietary patterns captured by the Healthy Eating Index (HEI) are associated with serum concentrations of sex steroid hormones and sex hormone-binding globulin (SHBG). OBJECTIVES: The objective is investigating the association between HEI and sex steroid hormones and SHBG in a general US population of men. METHODS: We used data on serum sex steroid hormones and SHBG levels, HEI, and other variables collected in the National Health and Nutrition Examination Survey (NHANES), 1999-2002. A total of 550 men >20 years old were included in the analysis. The cross-sectional associations between HEI (from 0 to 100 points, higher score equates to a healthier diet) with natural logarithm transformed concentrations of total and free testosterone, total and free estradiol, and SHBG were evaluated with multivariable linear regression models and adjusted for potential confounders. We also stratified by the body mass index (BMI) and race/ethnicity and tested for interactions. RESULTS: HEI showed a significant inverse association with free estradiol (p = 0.03), but was not associated with total or free testosterone, total estradiol, or SHBG concentrations. Neither BMI nor race/ethnicity statistically significantly modified the association between HEI and sex steroid hormone levels. CONCLUSION: The present cross-sectional analysis in a representative sample of US men showed no consistent association between eating habits, sex steroid hormones, and SHBG. Longitudinal studies are needed to further investigate potential associations.

Endogenous DNA damage and testicular germ cell tumors.

Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case-case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR(50th percentile) = 3.31, 95% CI: 1.00, 10.98; OR(75th percentile) = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR(50th percentile) = 2.27, 95% CI: 0.75, 6.87; OR(75th percentile) = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

Incidence of testicular tumor subtypes according to the updated WHO classification, North Rhine-Westphalia, Germany, 2008-2013.

BACKGROUND: In 2016, the WHO introduced an updated classification for testicular tumors. The application of this updated classification to cancer registry data requires some recoding of tumors. OBJECTIVES: The aim of this study was to provide up-to-date population-based incidence estimates of subtypes of testicular germ cell tumors (TGCT) according to the updated classification. MATERIAL AND METHODS: We reviewed 2251 pathology reports (42.9%) out of 5252 testicular tumors at the cancer registry of North Rhine-Westphalia for the years 2008-2013. We used population counts to estimate age-standardized incidence rates per million person-years (EUROSTAT revised European Standard Population). RESULTS: The application of the updated WHO classification resulted in a recoding of 8.9% of all testicular tumors. While the recodings have no influence on the incidence of seminomatous and non-seminomatous TGCTs that include mixed TGCTs, they influence the incidence of individual histological types of seminomatous and non-seminomatous TGCTs. Among the 4935 testicular germ cell tumors (TGCT), 23.7% were mixed TGCTs. Overall, 46.9% of all mixed TGCTs included seminoma and age-standardized incidence rates were highest for the combination seminoma plus embryonal carcinoma (5.9 per million person-years) and embryonal carcinoma plus teratoma (4.9 per million person-years). The median age at diagnosis was higher for mixed TGCTs including seminoma (31 years) than those that did not include seminoma (28 years). DISCUSSION AND CONCLUSIONS: Population-based incidence time trends for seminomatous and non-seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non-seminomatous TGCTs are examined.

Associations between circulating sex steroid hormones and leukocyte telomere length in men in the National Health and Nutrition Examination Survey.

Preliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age-related conditions. Therefore, we conducted a cross-sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999-2002 surveys). Sample-weighted linear regression analyses were conducted to assess age-adjusted and multivariable-adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (ßcontinuous per §IQR  = -61, p = 0.04; free estradiol ßcontinuous per §IQR  = -67, p = 0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol-induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length.

Marijuana use and serum testosterone concentrations among U.S. males.

Marijuana has been reported to have several effects on the male reproductive system. Marijuana has previously been linked to reduced adult testosterone, however, a study in Denmark reported increased testosterone concentrations among marijuana users. This study was performed to estimate the effect of marijuana use on testosterone in U.S. males. Data on serum testosterone, marijuana use, and covariates for 1577 men from the 2011-2012 U.S. National Health and Nutrition Examination Survey (NHANES) were analyzed. Information on marijuana use was collected by a self-administered computer-assisted questionnaire. Serum testosterone was determined using isotope dilution liquid chromatography tandem mass spectrometry. The effects of marijuana use on serum testosterone concentrations were examined by frequency, duration, and recency of use. Adjusted means and 95% confidence intervals (CI) of serum testosterone across levels of marijuana use were estimated using multiple linear regression weighted by the survey weights. The majority (66.2%) of the weighted study population reported ever using marijuana with 26.6% reporting current marijuana use. There was no difference in serum testosterone between ever users (adjusted mean = 3.69 ng/mL, 95% CI: 3.46, 3.93) and never users (adjusted mean = 3.70 ng/mL, 95% CI: 3.45, 3.98) upon multivariable analysis. However, serum testosterone was inversely associated with time since last regular use of marijuana (p-value for trend = 0.02). When restricted to men aged 18-29 years, this relationship strengthened (p-value for trend <0.01), and serum testosterone was also inversely associated with time since last use (p-value for trend <0.01), indicating that recency of use, and not duration or frequency, had the strongest relationship with testosterone levels. Serum testosterone concentrations were higher in men with more recent marijuana use. Studies are needed to determine the extent to which circulating testosterone concentrations mediate the relationship of marijuana use with male reproductive outcomes.