A prospective study of coffee intake and pancreatic cancer: results from the NIH-AARP Diet and Health Study.

BACKGROUND: Evidence evaluating the association between type of coffee intake (caffeinated, decaffeinated) and risk of pancreatic cancer is limited. METHODS: In the US NIH-AARP Diet and Health Study, we used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for coffee intake and risk of pancreatic cancer among 457 366 US adults. RESULTS: Over 4 155 256 person-years of follow-up, 1541 incident first primary pancreatic cancers occurred. Following detailed adjustment for tobacco smoking history, risk estimates for coffee drinking were not statistically significant; compared with never drinkers of coffee, the hazard ratios (95% CI) were 1.05 (0.85-1.30), 1.06 (0.86-1.31), 1.03 (0.85-1.25), 1.00 (0.79-1.25), and 1.24 (0.93-1.65) for <1, 1, 2-3, 4-5, and ≥6 cups per day, respectively (P-value for trend 0.46). The observed null association was consistent across all examined strata (sex, smoking status, coffee caffeination, and prevalent diabetes). CONCLUSIONS: In a prospective study of coffee intake with the largest number of pancreatic cancer cases to date, we did not observe an association between total, caffeinated, or decaffeinated coffee intake and pancreatic cancer.

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.

Away from home meals: associations with biomarkers of chronic disease and dietary intake in American adults, NHANES 2005-2010.

BACKGROUND: Away from home (AFH) meals are known to be energy-dense and of poor diet quality. Both direct and indirect exposure (for example, neighborhood restaurant density) to AFH meals have been implicated as contributors to higher body weight and adverse health outcomes. OBJECTIVE: To examine the association of frequency of eating AFH and fast-food meals with biomarkers of chronic disease and dietary intake. DESIGN: This cross-sectional study used frequency of AFH and fast-food meal and biomarker data from the NHANES 2005-2010. Information on weekly frequency of AFH and fast-food meals was collected via questionnaire during the household interview. The metabolic biomarkers examined included body mass index (BMI), serum cholesterol (total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)), triglycerides, glycohemoglobin and fasting glucose (n=8314, age⩾20, National Health and Nutrition Examination Surveys (NHANES) 2007-2010). Biomarkers of dietary exposure included serum concentrations of vitamins A, D, E, C, B-6, B-12, folate and carotenoids (n=4162; 2005-2006). Multiple linear and logistic regression methods adjusted for complex survey methodology and covariates. RESULTS: American adults reported a mean of 3.9 (95% confidence interval 3.7, 4.0) AFH and 1.8 (1.6, 1.9) fast-food meals/week. Over 50% of adults reported ⩾3 AFH and >35% reported ⩾2 fast-food meals/week. The mean BMI of more frequent AFH or fast-food meal reporters was higher (Ptrend⩽0.0004). Serum concentrations of total, LDL and HDL-cholesterol were related inversely with frequency of AFH meals (P<0.05). Frequencies of fast-food meals and serum HDL-cholesterol were also related inversely (P=0.0001). Serum concentrations of all examined micronutrients (except vitamin A and lycopene) declined with increasing frequency of AFH meals (P<0.05); women and ⩾50-year olds were at higher risk. CONCLUSIONS: Reporters of frequent AFH and fast-food meals had higher BMI and lower concentrations of HDL-cholesterol; however, profiles of other biomarkers did not indicate higher metabolic risk. However, the serum concentrations of nutrients with mostly plant foods as sources declined with increasing AFH meal frequency.

Estimating survival probabilities by exposure levels: utilizing vital statistics and complex survey data with mortality follow-up.

We present a two-step approach for estimating hazard rates and, consequently, survival probabilities, by levels of general categorical exposure. The resulting estimator utilizes three sources of data: vital statistics data and census data are used at the first step to estimate the overall hazard rate for a given combination of gender and age group, and cohort data constructed from a nationally representative complex survey with linked mortality records, are used at the second step to divide the overall hazard rate by exposure levels. We present an explicit expression for the resulting estimator and consider two methods for variance estimation that account for complex multistage sample design: (1) the leaving-one-out jackknife method, and (2) the Taylor linearization method, which provides an analytic formula for the variance estimator. The methods are illustrated with smoking and all-cause mortality data from the US National Health Interview Survey Linked Mortality Files, and the proposed estimator is compared with a previously studied crude hazard rate estimator that uses survey data only. The advantages of a two-step approach and possible extensions of the proposed estimator are discussed.

Extension of the Peters-Belson method to estimate health disparities among multiple groups using logistic regression with survey data.

Determining the extent of a disparity, if any, between groups of people, for example, race or gender, is of interest in many fields, including public health for medical treatment and prevention of disease. An observed difference in the mean outcome between an advantaged group (AG) and disadvantaged group (DG) can be due to differences in the distribution of relevant covariates. The Peters-Belson (PB) method fits a regression model with covariates to the AG to predict, for each DG member, their outcome measure as if they had been from the AG. The difference between the mean predicted and the mean observed outcomes of DG members is the (unexplained) disparity of interest. We focus on applying the PB method to estimate the disparity based on binary/multinomial/proportional odds logistic regression models using data collected from complex surveys with more than one DG. Estimators of the unexplained disparity, an analytic variance-covariance estimator that is based on the Taylor linearization variance-covariance estimation method, as well as a Wald test for testing a joint null hypothesis of zero for unexplained disparities between two or more minority groups and a majority group, are provided. Simulation studies with data selected from simple random sampling and cluster sampling, as well as the analyses of disparity in body mass index in the National Health and Nutrition Examination Survey 1999-2004, are conducted. Empirical results indicate that the Taylor linearization variance-covariance estimation is accurate and that the proposed Wald test maintains the nominal level.

Efficient analysis of case-control studies with sample weights.

Analysis of population-based case-control studies with complex sampling designs is challenging because the sample selection probabilities (and, therefore, the sample weights) depend on the response variable and covariates. Commonly, the design-consistent (weighted) estimators of the parameters of the population regression model are obtained by solving (sample) weighted estimating equations. Weighted estimators, however, are known to be inefficient when the weights are highly variable as is typical for case-control designs. In this paper, we propose two alternative estimators that have higher efficiency and smaller finite sample bias compared with the weighted estimator. Both methods incorporate the information included in the sample weights by modeling the sample expectation of the weights conditional on design variables. We discuss benefits and limitations of each of the two proposed estimators emphasizing efficiency and robustness. We compare the finite sample properties of the two new estimators and traditionally used weighted estimators with the use of simulated data under various sampling scenarios. We apply the methods to the U.S. Kidney Cancer Case-Control Study to identify risk factors. Published 2012. This article is a US Government work and is in the public domain in the USA.

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.

Delayed-type hypersensitivity in classic Kaposi sarcoma patients and controls.

BACKGROUND: Immune perturbation likely affects the development of Kaposi sarcoma (KS) among people infected with the KS-associated herpesvirus (KSHV). We tested whether KSHV-seropositive individuals or cases of classic KS (cKS), which typically originates in the leg, had differing delayed-type hypersensitivity (DTH) in the forearm or leg. METHODS: Mantoux DTH with three antigens (Candida, tetanus, PPD) was performed on the forearm and leg of 15 cKS cases, 14 KSHV-positives without KS, and 15 KSHV-negative controls. The diameters of induration responses were compared by group and body site. RESULTS: Leg DTH was greater than forearm DTH among controls (mean difference 5.6 mm, P=0.0004), whereas this was not observed in cKS cases (-2.2 mm, P=0.32) or KSHV-positives (0.5 mm, P=0.56). Leg-minus-forearm DTH difference was greater in controls compared with cKS cases (P=0.004) and KSHV-positives (P=0.002). Leg-plus-forearm DTH was similar in controls (mean 28.2 mm) and cKS cases (24.5 mm, P=0.60), but it was reduced in KSHV-positives (11.8 mm, P=0.02), particularly in the leg (P=0.004) and marginally in the forearm (P=0.07). CONCLUSION: KS cases had weaker DTH only in the leg, whereas both body sites appeared weaker in KSHV-positives without KS. Both systemic and regional immune alterations may influence the development of this malignancy.

Meat-cooking mutagens and risk of renal cell carcinoma.

BACKGROUND: High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case-control study conducted in metropolitan Detroit and Chicago. METHODS: Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database. RESULTS: The risk of RCC increased with intake of barbecued meat (P(trend)=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), P(trend)=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (P(interaction)<0.05). We found no association for HCAs or overall meat intake. CONCLUSION: BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC.

Risk of renal cell carcinoma in relation to blood telomere length in a population-based case-control study.

BACKGROUND: There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case-control studies suggested an association between short blood telomere length (TL) and increased RCC risk. METHODS: We conducted a large population-based case-control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models. RESULTS: Median TL was 0.85 for both cases and controls (P=0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (P<0.001 and P=0.07, respectively), and African Americans had longer TL than Caucasians (P<0.001). CONCLUSION: These data do not support the hypothesis that blood TL is associated with RCC. This population-based case-control study is, to our knowledge, the largest investigation to date of TL and RCC.

Family history of cancer and renal cell cancer risk in Caucasians and African Americans.

BACKGROUND: The association between renal cell carcinoma (RCC) risk and family history of cancer has not been examined with an adequate number of African Americans (AAs). METHODS: In a population-based case-control study, unconditional logistic regression was used to calculate the association between RCC risk and a family history of cancer among 1217 RCC cases and 1235 controls. RESULTS: Increased RCC risk was shown for subjects with at least one first-degree relative with kidney cancer (odds ratio=2.29; 95% confidence interval=1.31-4.00). No differences in risk were observed when analyses were stratified by race. For Caucasians, excess risk was observed among those reporting a sibling with kidney cancer, whereas for AAs, increased risk occurred among subjects reporting either a sibling or parent affected with the disease. A family history of non-renal cancers, and those related to smoking or to the von Hippel-Lindau syndrome, revealed no association with RCC risk. CONCLUSION: The RCC risk associated with a family history of kidney cancer is similar among Caucasians and AAs.

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.

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. METHODS: Among 52 158 women (aged 55-74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. RESULTS: Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00-1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03-1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02-1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. CONCLUSION: In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.

Joint associations of physical activity and sedentary behaviors with body mass index: results from a time use survey of US adults.

OBJECTIVE: Obesity risk is negatively associated with physical activity and positively associated with time spent in sedentary behaviors. Yet, it is not known how different combinations of sedentary and active behavior are associated with body mass index (BMI). This study examined the interaction between time spent in physical activity and sedentary behavior on BMI in US adults. DESIGN: Cross-sectional, data from the 2006 American Time Use Survey. SUBJECTS: 10 984 non-underweight adults (aged 21 + years). MEASUREMENT: A phone interview assessed all activities performed in the past 24 h, height, weight, health status, and other sociodemographic characteristics. Time spent in (1) moderate-to-vigorous leisure-time physical activity (MVPA), (2) active transportation (walking, biking), (3) sedentary leisure activities (TV/movie watching, computer use, playing games, reading), and (4) sedentary transportation (motorized vehicles) was determined from activity coding. BMI was calculated. RESULTS: After adjusting for age, gender, education level, race/ethnicity, and health status, sample-weighted linear regressions found significant interactions for leisure MVPA x TV/movies, leisure MVPA x playing games, active transportation x sedentary transportation, and active transportation x reading (Ps<0.0001). For example, the group of adults watching <60 min per day of TV/movies and engaging in > or =60 min per day of leisure MVPA had lower average BMI compared to the group watching <60 min per day of TV/movies and reporting <60 min per day of leisure MVPA (P<0.0001). In contrast, for adults watching > or =189 min per day of TV/movies, there was not a significant difference in BMI by time spent in leisure MVPA. CONCLUSION: Data from a US time use survey indicate that the strength of the association between certain types of sedentary behavior and BMI varies according to time spent in certain types of physical activity and vice versa.

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.

Past body mass index and risk of mortality among women.

BACKGROUND: Epidemiologic studies of body mass index (BMI) in relation to mortality commonly exclude persons with health conditions and/or a history of smoking to prevent bias resulting from illness-related weight loss ('reverse causation'). Analysis of BMI from an earlier time period may minimize reverse causation without requiring exclusion of participants based on disease or smoking history. METHODS: We prospectively examined BMI based on technician measurements of weight and height from 10 years prior to start of follow-up in relation to subsequent mortality in a cohort of 50 186 women who were 40-93 years old at baseline in 1987-1989. Deaths were ascertained through the US National Death Index. Proportional hazards regression was used to estimate hazard ratios (HRs) of mortality, adjusted for age, education, race/ethnicity, income, menopausal hormone use, smoking and physical activity. RESULTS: During 10 years of follow-up through 1997, 5201 women died. Overall, we observed a J-shaped association between BMI and mortality, with increased risk for women who were underweight, overweight or obese. The HRs and 95% confidence intervals of mortality for BMI categories of <18.5, 18.5-20.9, 21.0-23.4 (reference), 23.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-34.9 and 35.0+ kg m(-2) were 1.43 (1.19, 1.72), 1.07 (0.98, 1.17), 1.00 (reference), 1.10 (1.00, 1.20), 1.20 (1.11, 1.31), 1.23 (1.11, 1.37), 1.60 (1.44, 1.77) and 1.92 (1.64, 2.24). There was little evidence that pre-existing conditions (heart disease, diabetes and/or cancer) or smoking history modified the past BMI and mortality relation (P=0.54 and 0.76). CONCLUSIONS: In this large cohort of women, BMI based on technician measurements of weight and height from 10 years prior to baseline showed increased risk for mortality across the range of overweight and obesity, regardless of disease and smoking history. Observed associations between overweight, obesity and mortality in healthy individuals may also apply to persons with a history of disease or smoking.

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.