Search

Purpose: Pathways involving sex hormones and insulin-like growth factors (IGFs) have been proposed to explain, in part, the lower risk of prostate cancer among men with diabetes. To gain insights into potential biological mechanisms we explored differences in serum concentrations of sex hormones and IGFs across the trajectory from normoglycemia to prediabetes to poorly controlled diabetes., Methods: Using cross-sectional data from the National Health and Nutrition Examination Survey III we examined differences in levels of circulating sex hormones, sex hormone-binding globulin (SHBG), IGF-1, and IFG-binding protein 3 (IGFBP-3), according to diabetes status: no diabetes [n = 648], prediabetes [n = 578], undiagnosed diabetes [n = 106], well-controlled diabetes [n = 42], and poorly controlled diabetes [n = 56]. Adjusted geometric mean concentrations were derived using multivariable linear regression, adjusted for age, race, and other lifestyle factors., Results: Total testosterone concentrations were lower among prediabetics (4.89 ng/mL, 95% confidence interval (CI) 4.95-5.21) than men without prediabetes/diabetes (5.29 ng/mL, 95% CI 5.06-5.53) but did not reduce further across diabetes groups. Concentrations of estradiol, estimated free testosterone, SHGB, IGF-1, and IGFBP-3 did not differ. While the ratio of IGF-1 to IGFBP-3 was lower among men with prediabetics and undiagnosed diabetes than men without prediabetes/diabetes, there was no trend across groups. A positive trend for the ratio of estradiol-to-testosterone levels was observed across groups (p trend = 0.045)., Conclusion: Our findings do not provide clear support for either an androgen driven or IGF-driven pathway for the inverse association between diabetes and prostate cancer risk., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Obesity, underweight, and smoking are associated with an increased mortality. We investigated the joint effects of body mass index and smoking on all-cause and cause-specific mortality. Data of the Third National Health and Nutrition Examination Survey (1988-1994) including mortality follow-up until 2011 were used (n = 17,483). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), and cancer mortality with BMI, smoking, and their combinations as exposure, stratified by sex. Normal weight never smokers were considered as reference group. Compared to normal weight never smokers, obese and underweight current smokers were the two combinations with the highest mortality from all-causes, CVD, and cancer. Among underweight current smokers, the HR of death from all-causes was 3.49 (95% CI 2.42-5.02) and for obese current smokers 2.76 (2.12-3.58). All-cause mortality was particularly high in women who were underweight and current smoker (3.88 [2.47-6.09]). CVD mortality risk was the highest among obese current smokers (3.33 [2.98-5.33]). Cancer mortality risk was the highest among underweight current smokers (5.28 [2.68-10.38]). Obese current smokers in the middle age group (between 40 and 59 years old) had the highest risk of all-cause mortality (4.48 [2.94-7.97]). No statistically significant interaction between BMI and smoking on all-cause and cause-specific mortality was found. The current study indicates that obesity and underweight in combination with smoking may emerge as a serious public health problem. Hence, public health messages should stress the increased mortality risk for smokers who are underweight or obese. Also, health messages regarding healthy lifestyle are aimed at maintaining a healthy body weight rather than just "losing weight" and at not starting smoking at all.

Purpose: Telomere length at birth sets the baseline for telomere shortening and may influence adult disease risk like cancer. Telomere length is heritable, but may also be a marker of exposures in utero, including those influencing racial differences in risk. We examined racial differences in telomere length in maternal and umbilical cord blood from male neonates, and maternal-neonate correlations to generate hypotheses., Methods: Black and white pregnant women were recruited in 2006-2007 and followed to postpartum. Data came from questionnaires and medical records. Relative telomere length was measured by qPCR in leukocyte DNA. We estimated mean telomere length in mothers and neonates (n = 55 pairs) using linear regression and maternal-cord blood Spearman correlations, overall and by race., Results: Black mothers had shorter age- and plate-adjusted telomere length (2.49, 95% CI 2.11-2.86) than whites (2.92, 95% CI 2.63-3.22; p = 0.1) and black neonates had shorter telomere length (2.58, 95% CI 2.16-3.01) than whites (3.13, 95% CI 2.79-3.47; p = 0.1), though not statistically significant. Differences were attenuated after further adjustment for maternal factors. Maternal-cord blood correlations were moderate (r = 0.53, p < 0.0001), and did not differ by race., Conclusion: Telomere length may differ by race at birth due to both inherited and racial differences in maternal factors. This study was for hypothesis generation and results should be followed up in larger studies.

Purpose: To examine if dietary intake of foods rich in flavonoids, which have been shown to be inversely associated with chronic diseases, is associated with inflammatory processes., Methods: This analysis includes controls of case-control studies nested within the Multiethnic Cohort (MEC) who completed a validated food frequency questionnaire at cohort entry. Biomarkers were assessed in blood donated during follow-up (mean = 9.6 years). We used multivariate linear regression adjusted for potential confounders to estimate associations between intake of flavanones, flavonols, and isoflavones and levels of adiponectin, leptin, C-reactive protein, interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α., Results: Among the 1,287 participants, the respective median intakes of flavanones, flavonols, and isoflavones were 26.5, 12.4, and 1.3 mg/day at cohort entry. With the exception of flavanone intake, which was statistically significantly inversely associated with adiponectin (p = 0.01) and IL-6 concentrations (p = 0.01), none of the examined flavonoids was related with levels of adipokines or inflammatory markers. Heterogeneity by ethnicity was only observed for flavonol intake and IL-10 (p interaction  = 0.04) and may be the result of multiple testing. These null findings were confirmed in a subset of participants who completed a second dietary history within 2.6 years of blood draw., Conclusion: The current results do not support a consistent association between dietary intake of flavonoids and markers of inflammatory processes.

Purpose: To investigate differences in prostate cancer incidence between two distinct Swiss regions from 1996 to 2013 stratified by age group, grade, and T-stage., Methods: The dataset included 17,495 men living in Zurich and 3,505 men living in Ticino, diagnosed with prostate cancer between 1996 and 2013. We computed age-standardized incidence rates per 100,000 person-years using the European Standard Population. Trends were assessed using JoinPoint regression analysis Software., Results: Age-standardized incidence rates were generally higher in Zurich compared to Ticino but the difference decreased over time. Incidence rates increased significantly up to 2002 in Zurich and 2007 in Ticino and then decreased. A statistically significant increase was observed for men aged < 65 years, for grade 3 tumors, and for T-stage 2 and 3 tumors. The largest decrease was seen for grade 1 tumors. Furthermore, the incidence of tumors of unknown grade or T-stage decreased significantly in both regions., Conclusions: The trends in prostate cancer incidence rates were similar in both regions, although on a higher level in Zurich compared to Ticino. However, the difference decreased over time. The distribution of T-stage and grade did not explain the difference in incidence rates. Different use of opportunistic screening may play a role.

Background: By modulating the levels of sex steroid hormones and sex hormone-binding globulin (SHBG), caffeine could be a factor in the development of several conditions in men, including prostate cancer. The aim of this study was to evaluate if caffeine consumption is associated with concentrations of sex steroid hormones and SHBG in men., Methods: 1,410 men aged 20 + years who attended the morning examination session of the Third National Health and Nutrition Examination Survey (1988-1991) were included in the analysis. Coffee and soft drink consumption was assessed using a food frequency questionnaire. Daily caffeine intake was estimated by multiplying caffeine content per cup times the daily frequency of coffee, tea, or soft drink consumption. Serum levels of hormones and SHBG were measured by immunoassay. Associations of frequency of beverage consumption or estimated caffeine intake with hormone levels were examined using multivariable linear regression., Results: Coffee consumption was positively associated with SHBG concentration (p = 0.045) taking lifestyle factors into account, but mutually adjusting for testosterone and estradiol attenuated the association; no association with SHBG was observed for soft drink consumption or caffeine intake. No associations between caffeinated beverage consumption and androgen or estrogen concentrations were observed., Conclusion: Men who drink coffee more frequently may have higher circulating SHBG concentration, but there were no consistent associations for soft drinks or caffeine intake.

Purpose: Both low levels of vitamin D and of physical activity are associated with all-cause, cancer, and cardiovascular disease mortality. There is some evidence based on self-reported activity levels that physically more active individuals have higher vitamin D serum levels. The aim was to investigate associations between objectively measured and self-reported physical activity, respectively, and vitamin D serum concentrations in the US population., Methods: Data from NHANES 2003-2006 (n = 6,370, aged ≥ 18 years) were analyzed using multiple regression analyses. A total of 6,370 individuals aged 18 years and older with valid data on vitamin D serum levels and physical activity were included. Objective physical activity was assessed using accelerometers; self-reported physical activity was based on the NHANES physical activity questionnaire., Results: An increase of 10 min of objectively measured and self-reported moderate-to-vigorous activities per day was associated with an increase in circulating vitamin D of 0.32 ng/ml (95% CI 0.17, 0.48) and of 0.18 ng/ml (95% CI 0.12, 0.23), respectively. The odds ratio for being vitamin D deficient (< 20 ng/ml) if being insufficiently active compared with being sufficiently active was 1.32 (1.11, 1.57). Associations were not stronger for self-reported outdoor activities compared with indoor activities., Conclusions: Physical activity may be a way to achieve higher vitamin D serum levels in the population. Factors other than sun exposure that may be responsible for higher vitamin D levels in more active individuals need further investigation.

Purpose: Different prostate cancer mortality rates observed in European countries may depend on cultural background. We aimed at exploring variation in prostate cancer mortality in the language regions of Switzerland as a function of "Italianity", a proxy for adherence to an Italian lifestyle., Methods: We used data of the Swiss National Cohort, a census-based record linkage study, consisting of census (1990 and 2000) and mortality (until 2008) data. 1,163,271 Swiss and Italian nationals 40+-year old were included. Multivariate age-standardized prostate cancer mortality rates and hazard ratios (HR) from Cox proportional hazards regression analysis were performed. Italianity was defined by an individual's nationality, place of birth and principal language, resulting in a score of 0-3 points., Results: Age-standardized prostate cancer mortality rates (per 100,000 person-years) were lowest in the Italian-speaking region of Switzerland (66.7 vs. 87.3 in the German-speaking region). Both Italian nationality and/or place of birth were significantly associated with lower mortality. There was a graded inverse association between mortality rates and increasing Italianity score. Individuals with the highest level of Italianity had a HR of 0.67 (95 % CI 0.59-0.76) compared to those with an Italianity score of zero. Results were similar when looking at language regions separately., Conclusions: The strong and consistent association between Italianity and prostate cancer mortality suggests protective properties of an Italian lifestyle. Further research is required in order to determine which factors specific for Italian culture are responsible for the lower prostate cancer mortality.

Purpose: Chronic inflammation has been implicated in the etiology of various chronic diseases. We previously found that certain urinary isoflavones are associated with markers of inflammation. In the present study, we examined the associations of serum C-reactive protein (CRP) and white blood cell (WBC) count with lignans, which are more frequent in the Western diet than isoflavones., Methods: Our analysis included 2,028 participants of NHANES 2005-2008 and 2,628 participants of NHANES 1999-2004 aged 18 years and older. The exposures of interest were urinary mammalian lignans (enterodiol and enterolactone). Outcome variables were two inflammatory markers (CRP [≤10 mg/L] and WBC [≥3.0 and ≤11.7 (1,000 cells/μL)]). Log-transformed CRP concentration and WBC count by log-transformed creatinine-standardized concentrations of mammalian lignans were used for linear regression., Results: Statistically significant inverse associations of urinary lignan, enterodiol, and enterolactone concentrations with circulating CRP and WBC counts were observed in the multivariate-adjusted models: In NHANES 2005-2008, per one-percent increase in lignan concentrations in the urine, CRP concentrations and WBC counts decreased by 8.1 % (95 % CI -11.5, -4.5) and 1.9 % (95 % CI -2.7; -1.2), respectively. Per one-percent increase in enterodiol and enterolactone, WBC counts decreased by 2.1 % (95 % CI -2.8, -1.3) and 1.3 % (95 % CI -1.9, -0.6), respectively. In NHANES 1999-2004, analogous results were 3.0 % (95 % CI -5.6, -0.3), 1.2 % (95 % CI -2.0; -0.4), 1.0 % (95 % CI -1.8, -0.2), and 0.8 % (95 % CI -1.4, 0.2)., Conclusions: Mammalian lignans were inversely associated with markers of chronic inflammation. Due to the cross-sectional design, our findings require confirmation in prospective studies.

Purpose: Sex steroid hormone concentrations and insulin-like growth factor (IGF) proteins have been independently associated with risk of cancer, chronic diseases, and mortality. However, studies that evaluated the inter-relation between the sex hormones and IGF pathways have provided mixed results. We examined the association between endogenous sex hormones and sex hormone-binding globulin (SHBG) with IGF-1 and IGF-binding protein 3 (IGFBP-3) in a population-based sample of US men., Methods: Data from 1,135 men aged 20 years or older participating in the third National Health and Nutrition Examination Survey (NHANES III) were analyzed. Weighted linear regression was used to estimate geometric means and 95 % confidence intervals for IGF-1 and IGFBP-3 concentrations by sex steroid hormones and SHBG after adjusting for age, race/ethnicity, body mass index, waist circumference, alcohol consumption, cigarette smoking, physical activity, diabetes, and mutually adjusting for other sex hormones and SHBG., Results: No significant association was observed between sex steroid hormones, SHBG, and IGF-1 concentrations. Total estradiol (% difference in Q5 - Q1 geometric means -9.7 %; P-trend 0.05) and SHBG (% difference -7.3 %; P-trend 0.02) were modestly inversely associated with IGFBP-3. Total testosterone was modestly inversely associated with IGFBP-3 (% difference -6.2 %; P-trend 0.01), but this association disappeared after adjustment for total estradiol and SHBG (% difference 2.6 %; P-trend 0.23). Androstanediol glucuronide was not associated with IGFBP-3., Conclusions: These findings suggest that there may be inter-relationships between circulating total estradiol, SHBG, and IGFBP-3 concentrations. Future research may consider these inter-relationships when evaluating potential joint effects of the sex hormones and IGF pathways.

Purpose: The aim of this study was to determine the association between urinary isoflavonoid (genistein, daidzein, and the daidzein metabolites O-desmethylangolensin (O-DMA) and equol) excretion and markers of inflammation in adults in the United States in National Health and Nutrition Examination Survey (NHANES) 2005-2008., Methods: The NHANES is a cross-sectional study conducted by the National Center for Health Statistics to study the health and nutritional status of people living in the United States. The analysis included 1,683 participants from study years 2005-2008 for whom urinary isoflavonoids were measured and who met inclusion criteria. Urinary isoflavonoids were measured by HPLC-APPI-MS/MS. Serum C-reactive protein (CRP) was measured by latex-based nephelometry. White blood cell (WBC) count was measured by Coulter counting. Multivariable linear regression was used to calculate the geometric mean values of the markers, and multivariable logistic regression was used to estimate the odds of high CRP (≥3 mg/L) and of high WBC count (≥7,900/μL) by quartile of urinary isoflavonoid (nmol/mg creatinine)., Results: The highest quartile of genistein (OR = 0.62; 95 % CI 0.39-0.99) was associated with significantly decreased odds of high CRP compared with the lowest quartile. The sum of daidzein and its metabolites was significantly inversely associated with serum CRP concentration (p-trend = 0.017). Equol was inversely associated with WBC count (p-trend < 0.0001). O-DMA was the only isoflavonoid whose excretion was significantly associated with a decrease in both CRP (p-trend = 0.024) and WBC count (p-trend < 0.0001)., Conclusions: Though no clear pattern emerged, higher excretion of certain soy isoflavonoids was associated with decreased CRP concentration and WBC counts, suggesting a possible inverse association between soy intake and inflammation.

Objective: Contrary to the hypothesis that the racial/ethnic disparity in prostate cancer has a hormonal basis, we did not observe a difference in serum testosterone concentration between non-Hispanic black and white men in the Third National Health and Nutrition Examination Survey (NHANES III), although non-Hispanic black men had a higher estradiol level. Unexpectedly, Mexican-American men had the highest testosterone level. Next, we evaluated whether the same patterns are observed during adolescence, the time of prostate maturation., Methods: We measured serum testosterone, estradiol, and sex hormone-binding globulin (SHBG) by immunoassay in 134 males aged 12-19 in NHANES III. Mean concentrations were compared by race/ethnicity adjusting for age, Tanner stage, percent body fat, waist, physical activity, tobacco smoke, and the other hormones., Results: After multivariable adjustment, in the 12-15-year-old males, testosterone concentration was lower in non-Hispanic blacks than whites (p = 0.043), SHBG concentration did not significantly differ between the two groups. Mexican-Americans had the highest testosterone (versus non-Hispanic black: p = 0.002) and lowest SHBG (versus non-Hispanic white: p = 0.010; versus non-Hispanic black: p = 0.047) concentrations. Estradiol concentration was lower in non-Hispanic blacks (p = 0.11) and Mexican-Americans (p = 0.033) compared with non-Hispanic whites. After multivariable adjustment, in the 16-19-year-old males, testosterone, estradiol, and SHBG concentrations did not differ between non-Hispanic blacks and whites. Mexican-Americans had the highest testosterone concentration (versus non-Hispanic white: p = 0.08), but did not differ from the other groups on estradiol and SHBG concentrations. In both age groups, these patterns were generally present, but less pronounced after adjusting for age and Tanner stage only., Conclusion: In adolescent males, non-Hispanic blacks did not have a higher testosterone concentration than non-Hispanic whites, and Mexican-Americans had the highest testosterone concentration, patterns similar to adult males.

Aim: The aim of this study is to evaluate racial variation in umbilical cord blood concentration of vitamin D and to explore its correlation with markers of the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and black male neonates., Methods: In 2004-2005, venous umbilical cord blood samples were collected from 75 black and 38 white male neonates, along with maternal and birth characteristics from two hospitals in Maryland, United States. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured by radioimmunoassay and testosterone, estradiol, and sex hormone-binding globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed., Results: Mean 25(OH)D levels were lower in black than in white neonates (11.44; 95 % CI 10.10-12.95 ng/mL vs. 18.24; 95 % CI 15.32-21.72 ng/mL; p < 0.0001). Black neonates were at higher risk of suboptimal vitamin D levels [25(OH)D < 20 ng/mL] than whites (84 vs. 63 %). 25(OH)D concentrations varied by season in whites but not in blacks and were significantly inversely correlated with mother's parity (number of live births) in blacks but not in whites. Mean concentration of 1,25(OH)(2)D did not differ by race. 25(OH)D and 1,25(OH)(2)D did not correlate with IGFs, sex steroid hormones, and SHBG., Conclusions: Suboptimal vitamin D levels were prevalent especially in blacks and influenced by mother's parity and by season. The observed vitamin D differences between black and white neonates warrant further evaluation of the etiology of the disparity in chronic diseases in adulthood.

Background: Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC., Methods: A case-control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95 % confidence intervals (CI) were calculated by logistic regression analysis., Results: CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend = 0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p (Interaction) > 0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance., Conclusions: HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.

Purpose: To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis between female African-American and white neonates., Methods: Maternal and birth characteristics and venous umbilical cord blood samples were collected from 77 African-American and 41 white full-term uncomplicated births at two urban hospitals in 2004 and 2005. Cord blood was measured for testosterone, dehydroespiandrosterone-sulfate, estradiol, and sex steroid hormone-binding globulin (SHBG) by immunoassay. IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP-3) were measured by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed for the hormones., Results: African-American neonates weighed less at birth (3,228 g vs. 3,424 g, p < 0.004) than whites. Birth weight was positively correlated with IGF-1, IGFBP-3, and the molar ratio of IGF-1 to IGFBP-3, but inversely correlated with the molar ratio of IGF-2 to IGFBP-3. Adjusted models showed higher testosterone (1.82 ng/ml vs. 1.47 ng/ml, p = 0.006) and the molar ratio of testosterone to SHBG (0.42 vs. 0.30, p = 0.03) in African-American compared to white female neonates. IGF-1, IGF-2, and IGFBP-3 were lower in African-American compared to white female neonates, but only the difference for IGF-2 remained significant (496.5 ng/ml vs. 539.2 ng/ml, p = 0.04)., Conclusion: We provide evidence of racial variation in cord blood testosterone and testosterone to SHBG in African-American compared to white female neonates, and higher IGF-2 in white compared to African-American female neonates. Findings suggest plausible explanations for a prenatal influence on subsequent breast cancer risk and mortality. Further work is needed to confirm these observations.

To prospectively evaluate the associations of dietary calcium and magnesium intake with cancer incidence and mortality, data of 24,323 participants of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg), who were aged 35-64 years and cancer-free at recruitment (1994-1998), were analyzed using multivariate Cox regression models. After an average follow-up time of 11 years, 2,050 incident cancers were diagnosed and 513 cancer deaths occurred. Dietary calcium intake was inversely but not statistically significantly associated with colorectal cancer risk (hazard ratio [HR] for per 100 mg increase in intake: 0.95; 95% confidence interval [CI]: 0.88, 1.02) and lung cancer risk (HR for per 100 mg increase in intake: 0.94; 95% CI: 0.87, 1.02). No statistically significant associations were observed between dietary calcium intake and site-specific or overall cancer incidence or mortality. Dietary magnesium intake was not statistically significantly associated with any of the investigated outcomes. This prospective cohort study provides no strong evidence to support that high dietary calcium and magnesium intake in the intake range observed in a German population may reduce cancer incidence or mortality.

Objective: Obesity is associated with a variety of chronic diseases, including cancer, which may partly be explained by its influence on sex steroid hormone concentrations. Whether different measures of obesity, i.e., body mass index (BMI), waist circumference, and percent body fat were differentially associated with circulating levels of sex steroid hormones was examined in 1,265 men, aged 20-90+ years old, attending the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III)., Materials and Methods: Serum hormones were measured by immunoassay. Weight, height, and waist circumference were measured by trained staff. Percent body fat was estimated from bioelectrical impedance. Multivariate linear regression was used to estimate associations between body fatness measures and hormone levels., Results: Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all p trend < 0.05). The magnitude of change in these hormones was similar for a one-quartile increase in each body fatness measure., Conclusion: Measured BMI, waist circumference, and percent body fat led to similar inferences about their association with hormone levels in men.

Evidence from case-control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992-2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89-1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95-1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer.

Background: Vitamin E may protect against prostate cancer, possibly only in smokers and, we hypothesize, through altered sex steroid hormones. A controlled trial in smokers showed that sex hormone levels were inversely associated with baseline serum α-tocopherol and decreased in response to vitamin E supplementation. The vitamin E-hormone relation is understudied in non-smokers., Methods: Serum sex steroid hormones and α-tocopherol were measured for 1,457 men in NHANES III. Multivariable-adjusted geometric mean hormone concentrations by α-tocopherol quintile were estimated., Results: We observed lower mean testosterone, estradiol, and SHBG concentrations with increasing serum α-tocopherol (Q1 = 5.5 and Q5 = 4.6 ng/ml, p-trend = 0.0007; Q1 = 37.8 and Q5 = 33.1 pg/ml, p-trend = 0.02; Q1 = 38.8 and Q5 = 30.6 pg/ml, p-trend = 0.05, respectively). Interactions between serum α-tocopherol and exposure to cigarette smoke for total testosterone, total estradiol, and SHBG were found with the inverse relation observed only among smokers., Conclusions: Results from this nationally representative, cross-sectional study indicate an inverse association between serum α-tocopherol and circulating testosterone, estradiol, and SHBG, but only in men who smoked. Our findings support vitamin E selectively influencing sex hormones in smokers and afford possible mechanisms through which vitamin E may impact prostate cancer risk.

Background: Heterocyclic amines (HCA) are positively associated with prostate cancer risk in animal models. Because of mostly inconsistent results of epidemiological studies, we examined the association between intake of HCA and prostate cancer risk., Methods: In the EPIC-Heidelberg cohort, detailed information on diet, anthropometry, and lifestyle was assessed between 1994 and 1998. Dietary HCA intake was estimated using information on meat consumption, cooking methods, and preferred degree of browning. During 104,195 person-years of follow-up, 337 incident cases of prostate cancer (123 advanced cases) were identified among 9,578 men with valid dietary information. Multivariate Cox proportional hazards regression was used to examine the association between intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and prostate cancer., Results: Men in the highest quartiles of PhIP, MeIQx, and DiMeIQx intake, respectively, had no increased risk of prostate cancer compared with men in the lowest quartiles (HR = 0.89, 95% CI 0.66-1.22 [PhIP]; 1.06, 0.77-1.45 [MeIQx]; 0.98, 0.72-1.34 [DiMeIQx]). There were no associations between HCA intake and advanced prostate cancer or between high consumption of strongly browned meat and prostate cancer., Discussion: Our data do not support the hypothesis that HCA intake as consumed in a regular diet is a risk factor for prostate cancer.

Purpose: Low cholesterol levels and statin drugs may protect against prostate cancer with a worse prognosis. Their protective mechanism is unknown, but has been hypothesized to be related to cholesterol's role as a sex steroid hormone precursor. We evaluated whether serum testosterone and estradiol differ by cholesterol or cholesterol-lowering drug use., Materials and Methods: Testosterone and estradiol were measured for 1,457 male participants in the Third National Health and Nutrition Examination Survey. We estimated multivariable-adjusted geometric mean hormone concentration by quintiles of cholesterol concentration and by cholesterol-lowering drugs use., Results: Across quintiles of cholesterol, testosterone level did not differ (mean, 95% confidence interval (CI); Q1: 5.25, 5.02-5.49, Q5: 5.05, 4.76-5.37 ng/ml; p-trend = 0.32), whereas estradiol levels were lower (Q1: 38.7, 36.9-40.5; Q5: 33.1, 31.8-34.5 pg/ml; p-trend < 0.0001). Neither testosterone (no: 5.12, 4.94-5.30, yes: 4.91, 4.33-5.57 ng/ml, p = 0.57) nor estradiol (no: 35.9, 34.8-37.1; yes: 33.9, 29.4-39.2 pg/ml; p = 0.39) differed by cholesterol-lowering drugs use., Conclusion: Testosterone did not differ by cholesterol or cholesterol-lowering drug use. Estradiol was lower in men with higher cholesterol, but did not differ by cholesterol-lowering drug use. Our results suggest that the lower risk of advanced prostate cancer among statin users is not readily explained by a cholesterol-mediated effect of statins on sex hormone levels.

Objective: To analyse the association between types of physical activity (occupational, recreational and household, vigorous and overall) and risk of primary oesophageal (OAC) or gastric adenocarcinoma (GAC)., Methods: From nine European countries, 420,449 participants were recruited between 1991 and 2000 and followed-up for a mean of 8.8 years to register incident GAC and OAC. Information on physical activity (PA), diet, lifestyle and health-related variables was obtained at baseline. Helicobacter pylori infection status was considered in a subset of 1,211 participants. Analyses were repeated by tumour site (cardia/non-cardia) and histological type (intestinal/diffuse)., Results: During the follow-up, 410 GAC and 80 OAC occurred. A lower risk of overall and non-cardia GAC was found for increasing levels of a PA index which combined occupational PA with weekly time spent in sports and cycling. The hazard ratio (HR) of GAC was 0.69, 95% CI: 0.50-0.94, for the comparison between active and inactive participants according to the PA index (HR = 0.44, 95% CI:0.26-0.74, for non-cardia GAC). No effect was found for cardia tumours or histological subtypes of GAC. PA of any kind was not associated with OAC., Conclusions: Overall and distal (non-cardia) gastric tumours were inversely associated with time spent on cycling and sports and a total PA index. No association was found for any type of PA and risk of cardia cancers of the stomach.

Objective: To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study., Methods: Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors., Results: During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes., Conclusion: We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas.

Objective: We investigated the association of lifestyle and obesity with colorectal adenoma risk in a prospective setting., Methods: At recruitment (1994-1998), information on diet, anthropometry, lifestyle, and medication was assessed in 25,540 participants of the EPIC-Heidelberg cohort. Until June 2007, 536 verified incident colorectal adenomas were identified. Furthermore, participants with negative colonoscopy (n = 3966) were included in the analytic cohort., Results: In multivariate logistic regression analyses, participants with highest alcohol intake had an increased adenoma risk (odds ratio [OR] = 1.63; 95% CI 1.21-2.22) compared with lowest intake group. Folate consumption modified the ethanol effect (p-interaction = 0.03). Current smokers had a significantly increased adenoma risk compared with never smokers (OR = 1.40; 95% CI 1.16-1.84). Regular NSAID intake was associated with lower risk in subjects who reported their use at least twice compared with nonusers (OR = 0.70; 95% CI 0.53-0.93). Physical activity, body mass index, and waist-to-hip ratio were not consistently associated with adenoma risk., Conclusions: The results of this prospective cohort study showed that alcohol intake and smoking are important risk factors for colorectal adenoma, and regular NSAID use decreases the risk. The relationship between alcohol consumption and adenoma risk was modified by folate intake. However, we could not confirm an effect of obesity or physical activity on adenoma risk.

Background: We evaluated the associations of smoking, alcohol consumption, and physical activity with sex steroid hormone concentrations among 1,275 men > or =20 years old who participated in the Third National Health and Nutrition Examination Survey (NHANES III)., Methods: Serum concentrations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) were measured. We compared geometric mean concentrations across levels of smoking, alcohol, and physical activity using multiple linear regression., Results: Current smokers had higher total testosterone (5.42, 5.10, and 5.26 ng/ml in current, former, and never smokers), free testosterone (0.110, 0.102, and 0.104 ng/ml), total estradiol (40.0, 34.5, and 33.5 pg/ml), and free estradiol (1.05, 0.88, and 0.84 pg/ml) compared with former and never smokers (all p < or = 0.05). Men who consumed > or =1 drink/day had lower SHBG than men who drank less frequently (31.5 vs. 34.8 nmol/l, p = 0.01); total (p-trend = 0.08) and free testosterone (p-trend = 0.06) increased with number of drinks per day. Physical activity was positively associated with total (p-trend = 0.01) and free testosterone (p-trend = 0.05)., Conclusions: In this nationally representative sample of men, smoking, alcohol, and physical activity were associated with hormones and SHBG, thus these factors should be considered as possible confounders or upstream variables in studies of hormones and men's health, including prostate cancer.

Objective: To evaluate the association between lifestyle and dietary factors and serum concentrations of androgens in middle-aged healthy men., Methods: We conducted a cross-sectional analysis of the association of lifestyle factors with circulating concentrations of androstenedione (A-dione), 3-alpha-androstanediol glucuronide (A-diol-g), testosterone (T), SHBG (sex hormone-binding globulin), and free testosterone (FT) among 636 men in the European Prospective Investigation into Cancer and Nutrition., Results: Compared with the youngest age group (40-49 years), the oldest (70-79 years) had a higher mean concentration of SHBG (by 44%) and lower mean concentrations of A-diol-g (by 29%) FT (19%). Men in the highest BMI group (> or =29.83 kg/m(2)) had a higher mean A-diol-g concentration (by 38%) and lower mean concentration of T (by 20%) SHBG (29%) compared with the lowest (<24.16 kg/m(2)). Current smokers had higher mean concentrations of T (by 13%), SHBG (14%), and A-dione (15%) compared with never smokers. Physical activity and dietary factors were not associated with androgen concentrations, although men in the highest fifth of alcohol intake had higher mean concentrations of A-dione (by 9%), FT (11%) compared with the lowest., Conclusion: Our results suggest that age, body weight, smoking, and alcohol intake are associated with circulating androgen concentrations in men.

Objective: To examine the association of baseline and lifetime ethanol intake with cancer of the pancreas in the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: Included in this analysis were 478,400 subjects, of whom detailed information on the intake of alcoholic beverages at baseline and over lifetime was collected between 1992 and 2000. During a median follow-up time of 8.9 years, 555 non-endocrine pancreatic cancer cases were observed. Multivariate Cox proportional hazard models were used to examine the association of ethanol intake at recruitment and average lifetime ethanol intake and pancreatic cancer adjusting for smoking, height, weight, and history of diabetes., Results: Overall, neither ethanol intake at recruitment (relative risk (RR) = 0.94, 95% confidence interval (CI) 0.69-1.27 comparing 30+ g/d vs. 0.1-4.9 g/d) nor average lifetime ethanol intake (RR = 0.95, 95% CI 0.65-1.39) was associated with pancreatic cancer risk. High lifetime ethanol intake from spirits/liquor at recruitment tended to be associated with a higher risk (RR = 1.40, 95% CI 0.93-2.10 comparing 10+ g/d vs. 0.1-4.9 g/d), but no associations were observed for wine and beer consumption., Conclusion: These results suggest no association of alcohol consumption with the risk of pancreatic cancer.

Introduction: Lymphomas are a heterogeneous group of malignant diseases of cells of the immune system. The best-established risk factors are related to dys-regulation of immune function, and evidence suggests that factors such as dietary or lifestyle habits may be involved in the etiology., Material and Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 849 lymphoma cases were identified in a median follow-up period of 6.4 years. Fruit and vegetable consumption was estimated from validated dietary questionnaires. Cox proportional hazard models were used to examine the association between fruit and vegetable intake with the risk of lymphomas overall and subentities., Results: There was no overall association between total fruit and vegetable consumption and risk of lymphoma [hazard ratio (HR)=0.95, 95% confidence interval (CI) 0.78-1.15 comparing highest with lowest quartile]. However, the risk of diffuse large B-cell lymphomas (DLBCL) tended to be lower in participants with a high intake of total vegetables (HR=0.49, 95% CI 0.23-1.02)., Conclusion: In this large prospective study, an inverse associations between fruit and vegetable consumption and risk of lymphomas overall could not be confirmed. Associations with lymphoma subentities such as DLBCL warrant further investigation.

Objective: To examine the association between anthropometry and endometrial cancer, particularly by menopausal status and exogenous hormone use subgroups., Methods: Among 223,008 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during 6.4 years of follow-up. The analysis was performed with Cox proportional hazards modeling., Results: Weight, body mass index (BMI), waist and hip circumferences and waist-hip ratio (WHR) were strongly associated with increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30- < 40 kg/m(2)) compared to normal weight (BMI < 25) women was 1.78, 95% CI = 1.41-2.26, and for morbidly obese women (BMI > or = 40) was 3.02, 95% CI = 1.66-5.52. The RR for women with a waist circumference of > or =88 cm vs. <80 cm was 1.76, 95% CI = 1.42-2.19. Adult weight gain of > or =20 kg compared with stable weight (+/-3 kg) increased risk independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11-2.77). These associations were generally stronger for postmenopausal than premenopausal women, and oral contraceptives never-users than ever-users, and much stronger among never-users of hormone replacement therapy compared to ever-users., Conclusion: Obesity, abdominal adiposity, and adult weight gain were strongly associated with endometrial cancer risk. These associations were particularly evident among never-users of hormone replacement therapy.

Objective: To evaluate the association of meat and dairy food consumption with subsequent risk of prostate cancer., Methods: In 1989, 3,892 men 35+ years old, who participated in CLUE II study of Washington County, MD, completed an abbreviated Block food frequency questionnaire. Intake of meat and dairy related foods was calculated using consumption frequency and portion size. Incident prostate cancer cases (n = 199) were ascertained through October 2004. Cox proportional hazards regression was used to calculate hazard ratios (HR) of total and advanced (SEER states three and four; n = 54) prostate cancer and 95% confidence intervals (CI) adjusted for age, BMI at age 21, and intake of energy, saturated fat, and tomato products., Results: Intakes of total mean (HR = 0.90, 95% CI 0.60-1.33, comparing highest to lowest tertile) and red meat (HR = 0.87, 95% CI 0.59-1.32) were not statistically significantly associated with prostate cancer. However, processed meat consumption was associated with a non-statistically significant higher risk of total (5+ vs. < or =1 servings/week: HR = 2.24; 95% CI 0.90-5.59) prostate cancer. There was no association across tertiles of dairy or calcium with total prostate cancer, although compared tp < or =1 servings/week consumption of 5+ servings/week of dairy foods was associated with an increased risk of prostate cancer (HR = 1.65, 98% CI 1.02-2.66)., Conclusion: Overall, consumption of processed meat, but not total meat or red meat, was associated with a possible increased risk of total prostate cancer in this prospective study. Higher intake of dairy foods but not calcium was positively associated with prostate cancer. Further investigation into the mechanisms by which processed meat and dairy consumption might increase the risk of prostate cancer is suggested.

Objective: Most studies on tobacco smoking have focused on daily-smokers. Occasional smokers, who have never smoked daily, have often been included in the reference group of never-smokers. We have investigated the association between occasional smoking and cancer of the bladder, kidney, pancreas, upper aero-digestive tract and lung., Methods: The study population consisted of 158,488 persons, who provided information on occasional smoking, within the European Prospective Investigation into Cancer and Nutrition (EPIC), 780 of whom developed a smoking-related cancer. We used Cox proportional hazard model, stratified by gender and country to estimate incidence rate ratios (IRR) for smoking-related cancers., Results: The results suggest that occasional smokers have a higher risk of bladder cancer (IRR: 1.92, 95% confidence interval (CI) 0.93-3.98) and of the major smoking-related cancers combined (IRR: 1.24, 95% CI 0.80-1.94) than true never-smokers. Including occasional smokers in the reference group resulted in a lower risk estimate for former and current smokers., Conclusions: Occasional smoking should be discouraged.

Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (<120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.

Objectives: To evaluate the association of vasectomy with prostate cancer., Methods: Participants were male members of the CLUE II cohort followed since 1989. On a questionnaire mailed in 1996, the men were asked if they had had a vasectomy and their age at vasectomy. Between 1996 and April 2004, 78 prostate cancer cases were confirmed among the 3373 men who were at least 35 years old at baseline and who completed the questions about vasectomy. Cox proportional hazards regression was used to estimate age-adjusted hazard ratios (HR) of prostate cancer., Results: The HR for prostate cancer for men who had had a vasectomy was 2.03 (95% CI: 1.24-3.32). Risk of low-grade disease (HR=2.87; 95% CI 1.49-5.54), but not high-grade disease (HR=0.99; 95% CI 0.36-2.76), was higher in men who had had a vasectomy. No statistically significant associations were observed for low- or high-stage disease. The association for vasectomy was more pronounced in men who were 40 years at the time of vasectomy (HR=2.63; 95% CI 1.40-4.94) than in men who were younger at vasectomy., Conclusions: The results from this prospective study suggest a positive association between vasectomy and prostate cancer, especially low-grade disease.