Prospective Study Risk Research Articles

Association Between Treatment Modality and Probability of Second Malignancy in Localized Prostate Cancer Patients

<h3>Purpose/Objective(s)</h3> Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). Relative SM probabilities following stereotactic body radiotherapy (SBRT) or moderately hypofractionated radiation (HF-IMRT) remain unknown. We hypothesized that the probability of SM following SBRT or HF-IMRT would differ compared with conventionally fractionated intensity modulated radiotherapy (CF-IMRT). <h3>Materials/Methods</h3> Cohort analysis of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up compared SM probability amongst men receiving either radical prostatectomy (RP), CF-IMRT, HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models. Sensitivity analyses were conducted to evaluate differences in SM stratified by year of treatment and follow up length. Propensity score-adjusted pairwise assessments of modalities were also performed. <h3>Results</h3> For 303,432 patients, median follow-up was 9.08 years (IQR 7.01 – 11.21), and median age was 64 years (IQR 58–69). Crude rates of SM by treatment modality were: 5.2% for RP, 8.9% for CF-IMRT, 7.7% for HF-IMRT, 7.9% for BT, and 5.3% for SBRT. Adjusted odds ratios (AOR) for development of SM (referent: RP) were: CF-IMRT vs. RP 1.20 (95% CI 1.14–1.25, <i>P</i> < 0.001), HF-IMRT vs. RP 1.25 (95% CI 1.01–1.55, <i>P</i> = 0.045), BT vs. RP 1.11 (95% CI 1.07–1.16, <i>P</i> < 0.001), and SBRT vs. RP 0.95 (95% CI 0.81–1.12, <i>P</i> = 0.567). Sensitivity analyses confirmed higher probability of SM comparing CF-IMRT to RP (<i>P</i> < 0.01 for all) and no statistically significant difference comparing SBRT to RP at all year and follow-up length groupings (<i>P</i> = NS for all). On propensity score-adjusted analysis, SBRT was associated with lower probability of SM compared to CF-IMRT (AOR 0.78, 95% CI 0.66–0.93, <i>P</i> = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95% CI 0.73–1.03, <i>P</i> = 0.102). <h3>Conclusion</h3> Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy, but not stereotactic body radiotherapy, were associated with increased probability of a second malignancy compared to radical prostatectomy. Our findings underscore the need for assessment of second malignancy risk in prospective studies of SBRT.

Second malignancy probabilities in prostate cancer patients treated with SBRT and other contemporary radiation techniques

BackgroundProstate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). However, relative SM probabilities following treatment with contemporary radiation techniques such as stereotactic body radiotherapy (SBRT) or moderately hypofractionated intensity modulated radiotherapy (HF-IMRT) remain unknown. MethodsA cohort analysis was performed of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up comparing SM probability amongst men receiving either radical prostatectomy (RP), conventionally fractionated intensity-modulated radiotherapy (CF-IMRT), HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models, which were used to generate predicted probabilities. Additionally, propensity score-adjusted pairwise assessments of modalities were performed. ResultsFor 303,432 patients included in the study, median follow-up was 9.08 years (IQR 7.01–11.21). Predicted rates of SM by treatment modality and adjusted odds ratios (AOR) for development of SM (referent: RP) were: 6.0% for RP (AOR n/a), 7.1% for CF-IMRT (AOR 1.20, 95%CI 1.14–1.25, P < 0.001), 7.3% for HF-IMRT (AOR 1.25, 95%CI 1.01–1.55, P = 0.045), 6.6% for BT (AOR 1.11, 95%CI 1.07–1.16, P < 0.001), and 5.7% for SBRT (AOR 0.95, 95%CI 0.81–1.12, P = 0.567). On propensity score-adjusted analysis, SBRT was associated with lower odds of SM compared to CF-IMRT (AOR 0.78, 95%CI 0.66–0.93, P = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95%CI 0.73–1.03, P = 0.102). ConclusionsConventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy but not stereotactic body radiotherapy were associated with increased probability of a second malignancy compared to radical prostatectomy. Patients treated with SBRT may be at lower risk of second malignancy due to improved conformality, radiobiological differences or patient selection. The possibility that SBRT in select patients may minimize the probability of SM underscores the need for assessment of second malignancy risk in prospective studies of SBRT.

A Non-Probiotic Fermented Soy Product Reduces Total and LDL Cholesterol: A Randomized Controlled Crossover Trial.

Traditional Asian fermented soy food products are associated with reduced cardiovascular disease risk in prospective studies, but few randomized controlled trials have been conducted in at-risk populations. The aim of this study was to investigate the effect of a commercial non-probiotic fermented soy product on blood lipids in adults with cardiovascular risk biomarkers. In a randomized, crossover, intervention study, 27 men and women (aged 29–75 y) exhibiting at least two risk factors, consumed two packets (12.5 g each) daily of a fermented powdered soy product, or an isoenergic control powder made from germinated brown rice for 12 weeks each. The consumption of the fermented soy product resulted in a significantly greater mean change from baseline (compared to the germinated rice, all p < 0.05) in total cholesterol of −0.23 mmol/L (CI: −0.40, −0.06) compared with 0.14 mmol/L (CI: −0.03, 0.31), respectively; and low density lipoprotein (LDL) cholesterol −0.18 mmol/L (CI: −0.32, −0.04) compared with 0.04 mmol/L (CI: −0.01, 0.018) respectively. This was accompanied by an increase in high density lipoprotein (HDL) cholesterol in the germinated rice group, a decrease in apolipoprotein B (ApoB) in the fermented soy group, and a between-treatment effect in apolipoprotein A1 (ApoA1); however, the ratio of the LDL:HDL and of Apo B:ApoA1 did not differ between the groups. The ratio of total cholesterol:LDL decreased in men in the fermented soy group (p < 0.001). Twenty-four-hour urine collection at the end of each treatment period resulted in an increased excretion expressed as a ratio in μmol/d between treatments of 10.93 (CI: 5.07, 23.54) for daidzein; 1.24 (CI: 1.14, 4.43) for genistein; and, 8.48 (CI: 4.28, 16.80) for glycitein, all p < 0.05. The fermented soy powder consumed by participants in this study without implementing other changes in their typical diets, decreased the total and LDL cholesterol, and may serve as a dietary strategy to manage blood lipids. The trial was registered at ClinicalTrials.gov as NCT03429920.

Breakfast skipping and risk of cardiovascular disease: A systematic review and meta-analysis of prospective studies

AbstractBreakfast is considered to be the most important meal of the day, which significantly contributes to overall dietary quality. Global trends suggest a decline in breakfast consumption frequency in all age groups over the years. Breakfast skipping is associated with increased risk of weight gain, insulin resistance and type 2 diabetes, which are crucial risk factors of cardiovascular diseases (CVD). Regular breakfast consumption as a modifiable risk factor might be of great interest for cardiovascular prevention. Several prospective cohort studies showed contradictory findings on breakfast skipping and CVD risk. To the best knowledge of authors, this topic was not covered by any previous meta-analysis. Therefore, this review aimed to summarise the evidence on the association between breakfast skipping and CVD risk in prospective studies with particular emphasis on dose-response relationship and quality of existing evidence. A comprehensive search of the literature was performed using PubMed and Embase databases until February 2019, with no restriction to language and date. Inclusion criteria were as following: (1) participants aged ≥ 18 years, (2) prospective design, (3) information about breakfast consumption/skipping frequency and (4) outcome is the risk of CVD including coronary heart disease, stroke or heart failure. For high versus low comparison, random effects model was applied using the inverse variance method. Greenland-Longenecker method was used to conduct linear dose-response meta-analysis. Potential nonlinear association were examined using restricted cubic splines model. Heterogeneity was evaluated using the Cochrane Q test and I2 statistic with value &gt; 50% indicating substantial heterogeneity. Quality of evidence was assessed using NutriGrade tool. Out of 877 records identified in the literature search, four prospective cohort studies with 7258 CVD cases were included. Comparing breakfast skipping to regular breakfast consumption, there was a positive association with CVD risk (RR = 1.17 95%CI: 1.02–1.34, I2 = 39%, pheterogenity = 0.14). In linear dose-response meta-analysis, each additional day of breakfast skipping was related to 2% higher risk of CVD (RR = 1.02 95%CI: 1.00–1.04, I2 = 15%, pheterogenity = 0.31, n = 3). No non-linear association was observed (pnon-linearity = 0.53, n = 3). The quality of evidence for these associations was rated as low. This review indicated that breakfast skipping is associated with increased risk of CVD. Potential implementation of these findings in cardiovascular prevention has to consider low trust in existing evidence. Further prospective studies on this topic have to focus on the type of foods and meals consumed during breakfast, as well as BMI mediation.

Smoking, Helicobacter Pylori Serology, and Gastric Cancer Risk in Prospective Studies from China, Japan, and Korea.

Smoking is an established risk factor for gastric cancer development. In this study, we aimed to assess prospectively the association of smoking with gastric cancer risk in 1,446 non-cardia gastric cancer cases and 1,796 controls from China, Japan, and Korea with consideration of Helicobacter pylori infection as a potential effect modifier. Applying logistic regression models stratified by study and adjusted for age and sex we found that current, but not former, smoking was significantly associated with gastric cancer risk [OR = 1.33; 95% confidence interval (CI), 1.07-1.65]. However, the association was significant only in H. pylori sero-positive individuals determined by 3 different sero-markers: overall sero-positivity, sero-positivity to the onco-protein CagA, and sero-positivity to the gastric cancer associated sero-marker HP0305 and HP1564. Specifically, a significant interaction was found when stratifying by HP0305/HP1564 (P interaction = 0.01) with a 46% increased risk of gastric cancer among HP0305/HP1564 sero-positive current smokers (95% CI, 1.10-1.93) as opposed to no increased gastric cancer risk among HP0305/HP1564 sero-negative current smokers (OR = 0.93; 95% CI, 0.65-1.33). We confirmed that current smoking is associated with an increased gastric cancer risk, however, only among individuals that are simultaneously sero-positive for the leading causal factor for gastric cancer, H. pylori.

Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome—results from a 6-month, double-blind, randomized controlled trial

ABSTRACTBackgroundAnthocyanin-rich blueberry intake is associated with reduced type 2 diabetes and cardiovascular disease (CVD) risk in prospective studies, although long-term randomized controlled trials (RCTs) have not been conducted in at-risk populations.ObjectiveIn the longest-duration RCT to date, we examined the effect of 6-mo blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome.MethodsA double-blind, parallel RCT (n = 115; age 63 ± 7 y; 68% male; body mass index 31.2 ± 3.0 kg/m2) was conducted, which fed 2 dietarily achievable blueberry intakes [equivalent to 1/2 and 1 cup/d (75/150 g)] compared with matched placebo. Insulin resistance was assessed via the homeostasis model assessment of insulin resistance (primary endpoint) and confirmed by [6-6-2H2]-glucose-labeled, 2-step hyperinsulinemic clamp (n = 20). Clinically relevant cardiometabolic endpoints [including flow-mediated dilatation, augmentation index, lipoprotein status (by nuclear magnetic resonance spectroscopy), and nitric oxide (NO)-related metabolite assay] and anthocyanin metabolism were assessed.ResultsA daily intake of 1 cup of blueberries improved endothelial function (flow-mediated dilatation: +1.45%; 95% CI: 0.83%, 2.1%; P = 0.003), systemic arterial stiffness (augmentation index: –2.24%; 95% CI: –3.97%, –0.61%; P = 0.04) and attenuated cyclic guanosine monophosphate concentrations. In statin nonusers (n = 71), elevated high-density lipoprotein cholesterol (+0.08 mmol/L; P = 0.03), high-density lipoprotein particle density (+0.48n, ×10–6; P = 0.002) and apolipoprotein A-I (+0.05 g/L; P = 0.01) concentrations were observed following the 1-cup/d intervention. Treatment compliance was 94.1% (wrapper returns) and total concentrations of anthocyanin-derived phenolic acid metabolites significantly increased, dose-dependently, in serum and 24-h urine (P < 0.01 and P < 0.001, respectively). Insulin resistance, pulse wave velocity, blood pressure, NO, and overall plasma thiol status were unaffected. Likewise, a half cup per day had no effect on any biomarkers.ConclusionsDespite insulin resistance remaining unchanged we show, to our knowledge, the first sustained improvements in vascular function, lipid status, and underlying NO bioactivity following 1 cup blueberries/d. With effect sizes predictive of 12–15% reductions in CVD risk, blueberries should be included in dietary strategies to reduce individual and population CVD risk. This study was registered at clinicaltrials.gov as NCT02035592.

Breast cancer risk prediction in women aged 35\u201350\u2009years: impact of including sex hormone concentrations in the Gail model

BackgroundModels that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35–50.MethodsIn a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.ResultsThe AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.ConclusionsAMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35–50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.

Does Treating Vascular Risk Factors Prevent Dementia and Alzheimer's Disease? A Systematic Review and Meta-Analysis.

Epidemiological evidence has associated Alzheimer's disease (AD) with vascular risk factors (VRFs), but whether treatment of VRFs reduces the incidence of dementia and AD is uncertain. To conduct a systematic review and meta-analysis to summarize available data on the impact of treatment of VRFs on dementia and AD incidence. Pertinent studies published until 1 January 2018 were identified from PubMed. Both randomized controlled trials (RCT) and prospective studies that investigated the impact of treatment of VRFs on dementia or AD incidence were included. Eight RCTs and 52 prospective studies were identified. Antihypertensive treatment was associated with a non-significant reduced risk of dementia in RCTs (n = 5; relative risk [RR], 0.84; 95% confidence interval [CI], 0.69-1.02) and prospective studies (n = 3; RR, 0.77; 95% CI, 0.58-1.01) and with reduced AD risk in prospective studies (n = 5; RR = 0.78; 95% CI, 0.66-0.91). In prospective studies, treatment of hyperlipidemia with statins, but not nonstatin lipid-lowering agents, was associated with reduced risk of dementia (n = 17; RR, 0.77; 95% CI, 0.63-0.95) and AD (n = 13; RR, 0.86; 95% CI, 0.80-0.92). The single RCT on statins and dementia incidence showed no association. Data from one RCT and six prospective studies did not support a beneficial impact of antidiabetic drugs or insulin therapy on dementia risk. Current evidence indicates that antihypertensives and statins might reduce the incidence of dementia and AD. Further trials to determine the effect of VRF on AD are needed.

Robust Cox Regression as an Alternative Method to Estimate Adjusted Relative Risk in Prospective Studies with Common Outcomes

Objective: To demonstrate the use of robust Cox regression in estimating adjusted relative risks (and confidence intervals) when all participants with an identical follow-up time and when a common outcome is investigated. Methods: In this paper, we propose an alternative statistical method, robust Cox regression, to estimate adjusted relative risks in prospective studies. We use simulated cohort data to examine the suitability of robust Cox regression. Results: Robust Cox regression provides estimates that are equivalent to those of modified Poisson regression: regression coefficients, relative risks, 95% confidence intervals, P values. It also yields reasonable probabilities (bounded by 0 and 1). Unlike modified Poisson regression, robust Cox regression allows for four automatic variable selection methods, it directly computes adjusted relative risks for continuous variables, and is able to incorporate time-dependent covariates. Conclusion: Given the popularity of Cox regression in the medical and epidemiological literature, we believe that robust Cox regression may gain wider acceptance and application in the future. We recommend robust Cox regression as an alternative analytical tool to modified Poisson regression. In this study we demonstrated its utility to estimate adjusted relative risks for common outcomes in prospective studies with two or three waves of data collection (spaced similarly).

Serum CA 19-9 and risk of incident diabetes in middle-aged and elderly Chinese: a prospective cohort study.

Carbohydrate antigen (CA) 19-9 is a tumor marker for gastrointestinal and pancreatic cancers. Previous studies found that CA 19-9 was elevated in patients with diabetes, but little is known about its relationship with diabetes risk in prospective studies. Our objective was to evaluate the association between serum CA 19-9 and the risk of incident diabetes in Chinese population. Data were obtained from a prospective cohort study among 2391 middle-aged and elderly Chinese with a median follow-up of 3.8years. The measurement for the study outcome was incident diabetes. Compared with individuals in the lowest quartile, those in the highest quartile of CA 19-9 had significantly higher incidence of diabetes (12.54 vs. 8.86%, P=0.04). In the fully adjusted logistic regression model, compared with the lowest quartile, the highest quartile of CA 19-9 was significantly associated with 58% increased risk of incident diabetes [odds ratio (OR), 95% confidence interval (CI) 1.58, 1.02-2.44]. Stratified analysis suggested that the increased risk was seen only in women (OR, 95% CI 1.96, 1.10-3.48), or participants aged ≥65 (OR, 95% CI 2.32, 1.03-5.19), or those with body mass index ≥24 (OR, 95% CI 2.09, 1.20-3.63), or current nondrinkers (OR, 95% CI 1.79, 1.09-2.92), or those with impaired glucose regulation (IGR) (OR, 95% CI 2.49, 1.33-4.67). Significant interaction was detected between IGR and serum CA 19-9 (P for interaction <0.0001). Serum CA 19-9 is associated with a significantly increased risk of diabetes among the middle-aged and elderly Chinese population. Further investigations are needed to confirm this association and disclose potential mechanisms.

Circulating resistin levels and obesity-related cancer risk: A meta-analysis.

Resistin levels have been reported to be abnormal in obesity-related cancer patients with epidemiological studies yielding inconsistent results. Therefore, a meta-analysis was performed to assess the association between blood resistin levels and obesity-related cancer risk. A total of 13 studies were included for pooling ORs analysis. High resistin levels were found in cancer patients (OR= 1.20, 95% CI= 1.10-1.30). After excluding one study primarily contributing to between-study heterogeneity, the association between resistin levels and cancer risk was still significant (OR=1.18, 95% CI = 1.09-1.28). Stratification analysis found resistin levels were not associated with cancer risk in prospective studies. Meta-regression analysis identified factors such as geographic area, detection assay, or study design as confounders to between-study variance. The result of 18 studies of pooling measures on SMD analysis was that high resistin levels were associated with increased cancer risk (SMD = 0.94, 95% CI = 0.63-1.25), but not in the pooling SMD analysis of prospective studies. Except for the studies identified as major contributors to heterogeneity by Galbraith plot, resistin levels were still higher in cancer patients (SMD = 0.75, 95% CI = 0.63-0.87) in retrospective studies. Meta-regression analysis found factors, such as geographic area, BMI-match, size, and quality score, could account for 66.7% between-study variance in pooling SMD analysis of retrospective studies. Publication bias was not found in pooling ORs analysis. Our findings indicated high resistin levels were associated with increased obesity-related cancer risk. However, it may not be a predictor.

Chlamydia Trachomatis Infection-Associated Risk of Cervical Cancer: A Meta-Analysis.

As whether Chlamydia trachomatis infection increases the risk of cervical cancer is controversial in the literature, we performed a meta-analysis.Based on a comprehensive search of publications in the Medline, Cochrane, and EMBASE databases, we identified and extracted data from all relevant articles examining C. trachomatis infection and the risk of cervical cancer. The quality of each included study was assessed according to the 9-star Newcastle–Ottawa scale. The strength of association between the C. trachomatis and risk of cervical cancer was estimated by odds ratio (OR) and 95% confidence intervals (CIs). This review was registered at PROSPERO with registration No. CRD42014015672.A total of 22 studies with 4291 cervical cancer cases and 7628 controls were identified. Overall, C. trachomatis was significantly linked to increased cervical cancer risk in prospective studies (OR = 2.21, 95% CI: 1.88–2.61, P < 0.001), as well as in retrospective studies (OR = 2.19, 95% CI: 1.74–2.74, P < 0.001). Additionally, with a multivariate logistic regression analysis adjusted for HPV and age, C. trachomatis infection was identified as an independent predictor of cervical cancer in 11 studies (OR = 1.76, 95% CI: 1.03–3.01, P = 0.04). Coinfection of human papilloma virus and C. trachomatis has a higher risk of cervical cancer (OR = 4.03, 95% CI: 3.15–5.16, P < 0.001). A subgroup analysis based on histological type indicated an elevated risk for both squamous cell carcinoma (OR = 2.21, 95% CI: 2.00–2.45, P < 0.001), and adenocarcinoma (OR = 1.61, 95% CI: 1.21–2.15, P = 0.001), in associated with C. trachomatis. Subgroup analysis by where C. trachomatis infection was detected showed a significantly higher risk of cervical cancer associated with C. trachomatis infection detected in serum (OR = 2.20, 95% CI: 2.01–2.42, P < 0.001), cervical tissue blocks (OR = 2.88, 95% CI: 1.21–6.83, P = 0.02), and cervical secretion (OR = 2.71, 95% CI: 1.41–5.20, P = 0.003), especially in serum with no obvious heterogeneity.In conclusion, our novel data demonstrate that individuals infected with C. trachomatis have a higher risk of cervical cancer. Therefore, it is necessary to expand C. trachomatis infection screening and treat women with C. trachomatis promptly, particularly those with human papilloma virus infections. This approach will not only protect against pelvic inflammatory disease and infertility, but may also prevent cervical cancer.

Bioactive prolactin levels and risk of breast cancer: a nested case-control study.

Prolactin is a lactogenic hormone associated with breast cancer risk in prospective studies, which used immunoassays. The immunoassay captures multiple isoforms and may not fully reflect the biologic activity of prolactin relevant to breast carcinogenesis. We considered plasma bioactive prolactin levels measured by the Nb2 lymphoma cell bioassay, which is sensitive to the somatolactogenic activity of prolactin and growth hormone, within a nested case-control study of invasive breast cancer in the Nurses' Health Studies (NHS/NHSII). We also considered associations with breast cancer risk factors. We had bioassay measures on 1,329 cases and 1,329 controls. Bioassay levels were inversely associated with parity (4+ vs. 0 children = -18%, P = 0.01), body mass index (30+ vs. <22 kg/m(2) = -16%, P < 0.01), and age at menopause (53+ vs. 48 years = -18%, P = 0.03) and positively with family history of breast cancer (yes vs. no = 14%, P < 0.01). The relative risk (RR) comparing the top versus bottom quartile of bioassay levels was 1.19 [95% confidence intervals (CI), 0.94-1.51; Ptrend = 0.18]. The association was suggestively stronger for postmenopausal (RR = 1.36; 95% CI, 0.93-1.98; Ptrend = 0.12) versus premenopausal women (RR = 0.99; 95% CI, 0.71-1.37; Ptrend = 0.71). There was an association for cases diagnosed <4 years after blood draw (RR = 2.66; 95% CI, 1.45-4.89; Ptrend < 0.01), but not for cases diagnosed later. We did not observe differential associations by estrogen receptor status or other tumor characteristics. Our results show similar associations for prolactin levels measured by bioassay and by immunoassay with both breast cancer risk factors and risk. Future work examining risk prediction model of breast cancer can use the immunoassay to accurately characterize risk.

Assessing the interaction of respiration and heart rate in heart failure and controls using ambulatory Holter recordings

Breathing is a critical component of cardiopulmonary function, but few tools exist to evaluate respiration in ambulatory patients. Holter monitoring allows accurate diagnosis of a host of cardiac issues, and several investigators have demonstrated the ability to detect respiratory effort on the electrocardiogram. In this study we introduce a myogram signal derived from 12-lead, high frequency Holter as a means of detecting respiratory effort. Using the combined myogram and ECG signal, four novel variables were created: total number of Cheyne–Stokes episodes; the BWRatio, the ratio of power (above baseline) measured one second after peak-to-peak respiratory power, an assessment of the “shape” of the respiratory effort; DRR, the change in RR interval centering around peak inspiration; and minutes of synchronized breathing, a fixed ratio of heart beats to respiratory cycles. These variables were assessed in 24-hour recordings from three cohorts: healthy volunteers (n=33), heart failure subjects from the GISSI HF trial (n=383), and subjects receiving implantable defibrillators with severely depressed left ventricular function enrolled in the M2Risk trial (n=470). We observed a statistically significant 6-fold increase in the number of Cheyne–Stokes episodes (p=0.01 by ANOVA), decreases in BWRatio (p<0.001), as well as decrease in DRR in heart failure subjects; only minutes of synchronized breathing was not significantly decreased in heart failure. This study provides “proof of concept” that novel variables incorporating Holter-derived respiration can distinguish healthy subjects from heart failure. The utility of these variables for predicting heart failure, arrhythmia, and death risk in prospective studies needs to be assessed.

Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis

Objective To assess the association between leucocyte telomere length and risk of cardiovascular disease.Design Systematic review and meta-analysis.Data sources Studies published up to March 2014 identified through searches of Medline,...

Dietary Fiber Intake and Risk of First Stroke

Fiber intake is associated with reduced stroke risk in prospective studies, but no meta-analysis has been published to date. Multiple electronic databases were searched for healthy participant studies reporting fiber intake and incidence of first hemorrhagic or ischemic stroke, published between January 1990 and May 2012. Eight cohort studies from the United States, northern Europe, Australia, and Japan met inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke, with some evidence of heterogeneity between studies (I(2); relative risk per 7 g/day, 0.93; 95% confidence interval, 0.88-0.98; I(2)=59%). Soluble fiber intake, per 4 g/day, was not associated with stroke risk reduction with evidence of low heterogeneity between studies, relative risk 0.94 (95% confidence interval, 0.88-1.01; I(2)=21%). There were few studies reporting stroke risk in relation to insoluble fiber or fiber from cereals, fruit, or vegetables. Greater dietary fiber intake is significantly associated with lower risk of first stroke. Overall, findings support dietary recommendations to increase intake of total dietary fiber. However, a paucity of data on fiber from different foods precludes conclusions regarding the association between fiber type and stroke. There is a need for future studies to focus on fiber type and to examine risk for ischemic and hemorrhagic strokes separately.

Flavonoids Intake and Risk of Lung Cancer: A Meta-analysis

A number of studies have evaluated the association between flavonoids intake and lung cancer risk. However, results were inconsistent. To clarify the role of flavonoids in lung cancer, we conducted a meta-analysis on this topic. Two authors independently searched PubMed and EMBASE for studies regarding the association of flavonoids intake with lung cancer risk. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated by using random-effects model. Eight prospective studies and four case-control studies involving 5073 lung cancer cases and 237 981 non-cases were included in this meta-analysis. The combined results indicated a statistically significant association between highest flavonoids intake and reduced risk of developing lung cancer (RR = 0.76, 95% CI = 0.63-0.92). Furthermore, an increase in flavonoids intake of 20 mg/day was associated with a 10% decreased risk of developing lung cancer (RR = 0.90, 95% CI = 0.83-0.97). In stratified analyses, the highest flavonoids intake was significantly associated with decreased lung cancer risk in prospective studies, studies conducted in Finnish population, studies without adjustment for fruits and vegetables or vitamins, males, smokers and studies using dietary history interview for flavonoids intake estimation. Most subclasses of flavonoids were inversely associated with lung cancer except for hesperetin. Our data indicate that high or an increased intake of flavonoids is associated with reduced risk of lung cancer in some population but not in other population.

DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis

Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies. In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association was detected. The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years.

Urachal carcinoma: surgical and chemotherapeutic options

The urachal ligament is an embryologic remnant connecting the dome of the bladder to the umbilicus via the ligamentum commune. Autopsy series suggest that in approximately a third of subjects, the urachal remnant may persist with tubular or cystic structures. However, tumors of this site are extremely rare. Patients usually present with hematuria and upon imaging, have evidence of a cystic or solid structure in the bladder dome or in the bladder midline. If a biopsy confirms adenocarcinoma, these tumors should be considered an urachal cancer until proven otherwise. Although there are no prospective clinical trials reported to date, large single-institution reports suggest surgical resection with a partial cystectomy and en bloc resection of the urachal ligament with umbilicus as the treatment of choice in the setting of localized disease. Although there is currently no definitive role for neoadjuvant or adjuvant chemotherapy in this tumor, risk factors predicting progression may allow for the selection of patients at higher relapse risk for prospective studies. Unfortunately, there are many patients who present with metastatic disease that currently is not likely to be curable. There is no standard chemotherapy regimen for these patients; however, there is new-found hope with a currently accruing clinical trial exploring a 5-fluorouracil-based chemotherapy combination in this patient population.

Magnesium may mediate the favorable impact of whole grains on insulin sensitivity by acting as a mild calcium antagonist

Recent epidemiology has linked high consumption of whole grains with reduced risk for diabetes, coronary disease, stroke, and various types of cancer; there is reason to suspect that improved insulin sensitivity is largely responsible for this protection. This phenomenon may be partially explained by the lower glycemic indices of some whole grain food products in comparison to their fiber-depleted analogs. Nonetheless, the fact that whole wheat flour promotes insulin sensitivity relative to white flour – and yet has a near-identical glycemic index – suggests that certain nutrients or phytochemicals in whole wheat, depleted by the refining process, promote preservation of insulin sensitivity. Magnesium is a likely candidate in this regard; magnesium deficiency promotes insulin resistance in rodents and in humans, whereas supplemental magnesium has been found to prevent type 2 diabetes in rodent models of this syndrome, and to improve the insulin sensitivity of elderly or diabetic humans. Magnesium-rich diets as well as above-average serum magnesium are associated with reduced diabetes risk in prospective epidemiology, and with greater insulin sensitivity in cross-sectional studies; moreover, other types of magnesium-rich foods – dairy products, legumes, and nuts – have been linked to decreased diabetes risk in prospective studies. The biochemical role of magnesium in support of insulin function is still poorly understood. In light of evidence that magnesium can function as a mild natural calcium antagonist, it is interesting to note suggestive evidence that increases in intracellular free calcium may compromise the insulin responsiveness of adipocytes and skeletal muscle, and may indeed play a pathogenic role in the insulin resistance syndrome. Thus, it is proposed that some or all of the favorable impact of good magnesium status on insulin function may reflect antagonism of the induction or effects of increased intracellular free calcium. Further research concerning the potential health benefits of long-term magnesium supplementation is clearly warranted. These considerations, however, should not detract from efforts to better inform the public regarding the strong desirability of choosing whole grain products in preference to refined grains.