Theoretical attributable risk analysis and Disability Adjusted Life Years (DALYs) based on increased dairy consumption.

BACKGROUND: Identification of modifiable risk factors that may impact chronic disease risk is critical to public health. Our study objective was to conduct a theoretical population attributable risk analysis to estimate the burden of disease from low dairy intake and to estimate the impact of increased dairy intake on United States (US)-based disability adjusted life years (DALYs). METHODS: We conducted a comprehensive literature review to identify statistically significant summary relative risk estimates (SRREs) from recent meta-analyses of dairy consumption and key chronic disease outcomes. The SRREs were applied to preventive fractions using a range of categories (low to high) for population consumption of dairy products. The preventive fraction estimates were then applied to the number of DALYs for each health outcome in the US based on 2019 WHO estimates. The population attributable risk proportion estimates were calculated using the inverse of the SRRE from each meta-analysis using the same range of categories of consumption. These values were subsequently applied to the DALYs estimates to estimate the theoretical burden of disease attributable to low dairy intake. RESULTS: Statistically significant SRREs were identified in recent meta-analyses of total dairy consumption in relation to breast cancer, colorectal cancer, cardiovascular disease (CVD), type 2 diabetes (T2D), stroke, and hypertension. In this theoretical analysis, nearly 850,000 DALYs (or 5.0% of estimated years of healthy life lost) due to CVD and 200,000 DALYs (4.5%) due to T2D may be prevented by increased dairy consumption. Approximately 100,000 DALYs due to breast cancer (7.5%) and approximately 120,000 DALYs (8.5%) due to colorectal cancer may be prevented by high dairy intake. The numbers of DALYs for stroke and hypertension that may be prevented by increased dairy consumption were approximately 210,000 (6.0%) and 74,000 (5.5%), respectively. CONCLUSIONS: Consumption of dairy products has been associated with decreased risk of multiple chronic diseases of significant public health importance. The burden of disease that may potentially be prevented by increasing dairy consumption is substantial, and population-wide improvement in meeting recommended daily dairy intake goals could have a notable public health impact. However, this analysis is theoretical, and thus additional studies providing empirical evidence are needed to further clarify potential relationships between dairy intake and various health outcomes.

Epidemiology of lung cancer among acrylonitrile-exposed study populations: A meta-analysis.

PURPOSE: To conduct a systematic review and meta-analysis of lung cancer among acrylonitrile-exposed workers. METHODS: A literature search through April 2020 was performed to identify relevant cohort and case-control studies. Data from these studies were meta-analyzed to generate summary relative risk estimates (SRREs). Heterogeneity was examined in sub-group and sensitivity analyses, and by meta-regression. RESULTS: Twenty-two studies were reviewed systematically, and 10 cohort studies and one case-control study were meta-analyzed. Individual relative risk estimates reported across studies were heterogeneous, with most being relatively weak in statistical strength and non-statistically significant on both sides of the null value. Meta-analysis of these data resulted in an SRRE of 1.04 (95% CI: 0.89-1.21; overall model, largely consisting of all workers exposed to acrylonitrile). Sub-group analyses and meta-regression did not support patterns of positive dose-response relationships by duration of exposure/employment or cumulative exposure. CONCLUSIONS: Although some positive associations have been reported in internal comparison analyses based on increasing exposure categories, few associations are statistically significant, there are no apparent or consistent patterns of dose-response, and the confounding influence of cigarette smoking was not adequately controlled. Thus, findings from this review and meta-analysis do not support an increased risk of lung cancer among acrylonitrile workers.

A Systematic Literature Review and Meta-Analysis Describing the Prevalence of KRAS, NRAS, and BRAF Gene Mutations in Metastatic Colorectal Cancer.

BACKGROUND: Tumors of the metastatic colorectal cancer (mCRC) patients that are wildtype (WT) for KRAS or NRAS mutations respond more favorably to anti-epidermal growth factor receptor (EGFR) treatments. Treatment guidelines now recommend that all mCRC patients have WT KRAS and NRAS tumor status confirmed prior to initiating anti-EGFR therapy. Evidence also suggests that BRAF mutations may predict lack of response to anti-EGFR therapy. As such, there is now a need for comprehensive data on the prevalence of KRAS, NRAS, and BRAF mutations among patients with mCRC. METHODS: A systematic literature review was conducted among studies that described the prevalence of KRAS, NRAS, and BRAF gene mutations in mCRC patients. Observational cohort studies and standard of care arm of randomized clinical trials were included. Random effects meta-analysis models were used to create summary prevalence estimates for each of the mutation types. Subgroup analyses were also conducted to identify potential sources of heterogeneity. Exploratory analyses of overall and progression-free survival by mutation status were also conducted. RESULTS: This systematic review and meta-analysis included 275 studies comprising 77,104 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males, and significant variation by study location was observed for both KRAS and BRAF mutation prevalence. Overall survival was significantly decreased for patients with KRAS, BRAF, and NRAS mutations compared to those with WT tumors. Progression-free survival was also significantly decreased among patients with KRAS and BRAF mutations. CONCLUSIONS: KRAS, NRAS, and BRAF mutation statuses in patients with mCRC are important predictors of treatment success and may also have prognostic value. In this paper we present the first systematic and comprehensive literature review and meta-analysis of the prevalence of KRAS, BRAF, and NRAS mutations and demonstrate the prognostic impact of mutation status on survival.

The incidence of infusion reactions associated with monoclonal antibody drugs targeting the epidermal growth factor receptor in metastatic colorectal cancer patients: A systematic literature review and meta-analysis of patient and study characteristics.

BACKGROUND: Systemic cancer therapies may induce infusion reactions (IRs) or hypersensitivities. Metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies, including cetuximab and panitumumab, may be subject to these reactions. We conducted a meta-analysis to estimate the IR incidence in this population and identify variations in this incidence by patient or study characteristics. METHODS: A systematic review was conducted to identify observational studies or clinical trials of mCRC patients treated with anti-EGFR therapies that reported occurrences of IRs, hypersensitivity, or allergy/anaphylaxis. The objective of the study was to estimate the incidence of IRs. Random effects models were used to meta-analyze the incidence of IRs overall and stratified by therapy type, study design, geographic location, RAS or KRAS mutation status, grade of reaction severity, and terminology used to describe the reaction. RESULTS: The pooled estimate for IR incidence was 4.9% (95% confidence interval: 3.6%-6.5%). Lower-grade reactions were more common than higher-grade reactions overall and the incidence of reactions among cetuximab patients was nearly four times that of panitumumab patients (6.1% vs 1.6%). CONCLUSIONS: IRs occur in approximately 5% of mCRC patients treated with anti-EGFR therapies, and the incidence varies significantly by grade of severity and therapy type. Studies evaluating these outcomes should consider investigating survival outcomes by IR status to determine its prognostic relevance.

Factors Associated with Breastfeeding Initiation and Continuation: A Meta-Analysis.

OBJECTIVE: To use a quantitative approach to evaluate the literature for quantity, quality, and consistency of studies of maternal and infant characteristics in association with breastfeeding initiation and continuation, and to conduct a meta-analysis to produce summary relative risks (RRs) for selected factors. STUDY DESIGN: A systematic review using PubMed and CINAHL through March 2016 was conducted to identify relevant observational studies in developed nations, reporting a measure of risk for 1 or more of 6 quantitatively derived, high impact factors in relation to either breastfeeding initiation or continuation. One author abstracted data using a predesigned database, which was reviewed by a second independent author; data evaluation and interpretation included all co-authors. These factors were summarized using standard meta-analysis techniques. RESULTS: Six high impact factors were identified (smoking [39 papers], mode of delivery [47 papers], parity [31 papers], dyad separation [17 papers], maternal education [62 papers], and maternal breastfeeding education [32 papers]). Summary RR from random-effects models for breastfeeding initiation were highest for high vs low maternal education (RR 2.28 [95% CI 1.92-2.70]), dyad connection vs not (RR 2.01 [95% CI 1.38-2.92]), and maternal nonsmoking vs smoking (RR = 1.76 [95% CI 1.59-1.95]); results were similar for breastfeeding continuation. CONCLUSIONS: Despite methodological heterogeneity across studies, relatively consistent results were observed for these perinatally identifiable factors associated with breastfeeding initiation and continuation, which may be informative in developing targeted interventions to provide education and support for successful breastfeeding in more families.

Indirect treatment comparison of cabazitaxel for patients with metastatic castrate-resistant prostate cancer who have been previously treated with a docetaxel-containing regimen.

BACKGROUND: The objective of this study was to conduct an indirect treatment comparison between cabazitaxel, abiraterone and enzalutamide to determine the clinical efficacy and safety of cabazitaxel relative to comparators in the treatment of patients with metastatic castrate-resistant prostate cancer who progress on docetaxel-based therapies. METHODS: A systematic literature review was conducted to inform the network meta-analysis of cabazitaxel, abiraterone and enzalutamide. Due to a lack of head-to-head trials, studies with a comparator arm of best supportive care were included in the analysis. Overall survival, progression-free survival, and adverse events were compared within both Bayesian and Frequentist frameworks. The ratios for survival outcomes were estimated using hazard ratios (HR), and the ratios for adverse events between groups were estimated using odds ratios (ORs); uncertainty was reported as 95% confidence (Frequentist) and credible (Baysesian) Intervals. RESULTS: Three of thirteen trials identified for abstraction were relevant for analyses. Median overall survival was not statistically significantly different for abiraterone (HR = 1.04; 95% CI = 0.83-1.28) or enzalutamide (HR = 0.88; 95% CI = 0.69-1.11) when compared to cabazitaxel in the Bayesian analysis. Anaemia (OR = 3.71; 95% CI = 1.01-10.44), diarrhoea (OR = 16.60; 95% CI = 1.41-75.31) and haematuria (OR = 3.88; 95% CI = 1.03-10.09) were more likely to occur in the cabazitaxel group than the abiraterone group, while pyrexia risk was higher in cabazitaxel compared to enzalutamide (OR = 36.23; 95% CI = 1.14-206.40). Frequentist analyses produced similar results. CONCLUSIONS: The scarcity of clinical studies and lack of a common comparator limited analyses. The adverse event results must be interpreted with caution as many were based on small numbers. The results from this analysis indicate comparable survival outcomes and adverse event profiles. As these pivotal studies may not reflect the contemporary treatment landscape and patient profiles, additional research, including head-to-head clinical trials and real world observational studies, should be conducted to further elucidate the beneficial effects of these therapies.

Nutritional and health benefits of semi-elemental diets: A comprehensive summary of the literature.

AIM: To critically review and summarize the literature on nutritional and health outcomes of semi-elemental formulations on various nutritionally vulnerable patient populations who are unable to achieve adequate nutrition from standard oral diets. METHODS: We conducted a comprehensive literature search of Pubmed and Embase databases. We manually screened articles that examined nutritional and health outcomes (e.g., growth, disease activity, gastrointestinal impairment, mortality, and economic impact) among various patient groups receiving semi-elemental diets. This review focused on full-text articles of randomized controlled clinical trials and other intervention studies, but pertinent abstracts and case studies were also included. Results pertaining primarily to tolerance, digestion, and absorption were summarized for each patient population in this systematic review. RESULTS: Results pertaining primarily to tolerance, digestion, and absorption were summarized for each patient population. The efficacy of semi-elemental whey hydrolyzed protein (WHP) diet have been reported in various nutritionally high risk patient populations including - Crohn's disease, short bowel syndrome, acute and chronic pancreatitis, cerebral palsy, cystic fibrosis, cerebrovascular accidents, human immunodeficiency virus, critically ill, and geriatrics. Collectively, the evidence from the medical literature indicates that feeding with a semi-elemental diet performs as well or better than parenteral or amino acid based diets in terms of tolerance, digestion, and nutrient assimilation measures across various disease conditions. CONCLUSION: Based on this comprehensive review of the literature, patient populations who have difficulty digesting or absorbing standard diets may be able to achieve improved health and nutritional outcomes through the use of semi-elemental WHP diets.

Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis.

BACKGROUND: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis. METHODS: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I (2) estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures. RESULTS: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H <0.001, I (2) = 62.90). A similar SRRE was observed among the five Tier 1 studies with the highest quality ratings (SRRE = 0.76, 95% CI: 0.46-1.25), with no heterogeneity among studies (P-H = 0.912, I (2) = 0.00). Meta-analysis of the Tier 2 (n = 5) and Tier 3 (n = 6) studies resulted in SRREs of 1.09 (95% CI: 0.76-1.58) and 0.73 (95% CI: 0.49-1.08), respectively. Restricting the analysis to Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72-1.29). The SRRE specific to brake work (n = 4) was 0.64 (95% CI: 0.38-1.09). CONCLUSIONS: This meta-analysis of the epidemiologic studies provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma.

A review and meta-analysis of prospective studies of red and processed meat, meat cooking methods, heme iron, heterocyclic amines and prostate cancer.

Prostate cancer remains a significant public health concern among men in the U.S. and worldwide. Epidemiologic studies have generally produced inconclusive results for dietary risk factors for prostate cancer, including consumption of red and processed meats. We aimed to update a previous meta-analysis of prospective cohorts of red and processed meats and prostate cancer with the inclusion of new and updated cohort studies, as well as evaluate meat cooking methods, heme iron, and heterocyclic amine (HCA) intake exposure data. A comprehensive literature search was performed and 26 publications from 19 different cohort studies were included. Random effects models were used to calculate summary relative risk estimates (SRREs) for high vs. low exposure categories. Additionally, meta-regression analyses and stratified intake analyses were conducted to evaluate dose-response relationships. The SRREs for total prostate cancer and total red meat consumption, fresh red meat consumption, and processed meat consumption were 1.02 (95% CI: 0.92-1.12), 1.06 (95% CI: 0.97-1.16), and 1.05 (95% CI: 1.01-1.10), respectively. Analyses were also conducted for the outcomes of non-advanced, advanced, and fatal prostate cancer when sufficient data were available, but these analyses did not produce significant results. No significant SRREs were observed for any of the meat cooking methods, HCA, or heme iron analyses. Dose-response analyses did not reveal significant patterns of associations between red or processed meat and prostate cancer. In conclusion, the results from our analyses do not support an association between red meat or processed consumption and prostate cancer, although we observed a weak positive summary estimate for processed meats.

Red Meat and Colorectal Cancer: A Quantitative Update on the State of the Epidemiologic Science.

The potential relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate. Given the high degree of resulting uncertainty, our objective was to update the state of the science by conducting a systematic quantitative assessment of the epidemiologic literature. Specifically, we updated and expanded our previous meta-analysis by integrating data from new prospective cohort studies and conducting a broader evaluation of the relative risk estimates by specific intake categories. Data from 27 independent prospective cohort studies were meta-analyzed using random-effects models, and sources of potential heterogeneity were examined through subgroup and sensitivity analyses. In addition, a comprehensive evaluation of potential dose-response patterns was conducted. In the meta-analysis of all cohorts, a weakly elevated summary relative risk was observed (1.11, 95% CI: 1.03-1.19); however, statistically significant heterogeneity was present. In general, summary associations were attenuated (closer to the null and less heterogeneous) in models that isolated fresh red meat (from processed meat), adjusted for more relevant factors, analyzed women only, and were conducted in countries outside of the United States. Furthermore, no clear patterns of dose-response were apparent. In conclusion, the state of the epidemiologic science on red meat consumption and CRC is best described in terms of weak associations, heterogeneity, an inability to disentangle effects from other dietary and lifestyle factors, lack of a clear dose-response effect, and weakening evidence over time. KEY TEACHING POINTS: •The role of red meat consumption in colorectal cancer risk has been widely contested among the scientific community.•In the current meta-analysis of red meat intake and colorectal cancer, we comprehensively examined associations by creating numerous sub-group stratifications, conducting extensive sensitivity analyses, and evaluating dose-response using several different methods.•Overall, all summary associations were weak in magnitude with no clear dose-response patterns.•Interpretation of findings from epidemiologic studies investigating diet and health outcomes involves numerous methodological considerations, such as accurately measuring food intake, dietary pattern differences across populations, food definitions, outcome classifications, bias and confounding, multicollinearity, biological mechanisms, genetic variation in metabolizing enzymes, and differences in analytical metrics and statistical testing parameters.

Meta-Analysis of Long-Chain Omega-3 Polyunsaturated Fatty Acids (LCω-3PUFA) and Prostate Cancer.

We conducted a systematic review and meta-analysis to estimate the potential association between LCω-3PUFAs and prostate cancer (PC). A comprehensive literature search was performed through 2013 to identify prospective studies that examined dietary intakes of long-chain omega-3 polyunsaturated fatty acids (LCω-3PUFA) or blood biomarkers of LCω-3PUFA status and risk of PC. Random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for LCω-3PUFAs and total PC, and by stage and grade. Subgroup analyses were also conducted for specific fatty acids and other study characteristics. Twelve self-reported dietary intake and 9 biomarker studies from independent study populations were included in the analysis, with 446,243 and 14,897 total participants, respectively. No association between LCω-3PUFAs and total PC was observed (SRRE = 1.00, 95% CI: 0.93-1.09) for the dietary intake studies (high vs. low LCω-3PUFAs category comparison) or for the biomarker studies (SRRE of 1.07, 95% CI: 0.94-1.20). In general, most summary associations for the dietary intake studies were in the inverse direction, whereas the majority of summary associations for the biomarker studies were in the positive direction, but all were weak in magnitude. The results from this meta-analysis do not support an association between LCω-3PUFAs and PC.

Historical cancer incidence and mortality assessment in an Illinois community proximal to a former manufactured gas plant.

OBJECTIVES: Concern has been raised that the occurrence of cancer may be increased in neighbourhoods around a former manufactured gas plant in Champaign, Illinois, USA. Thus, we compared historical rates of cancer in this area to comparison communities as well as with nationally standardised rates. DESIGN: Retrospective population-based community cancer assessment during 1990-2010. SETTING: Champaign County, Illinois, USA, and zip codes encompassing the location of the former manufactured gas plant to counties that were similar demographically. PARTICIPANTS: Residents of the counties and zip codes studied between 1990 and 2010. MAIN OUTCOME MEASURES: The relative risk (RR) and 95% CI were used to compare cancer incidence and mortality in the areas near the gas compression site to the comparison counties. Standardised incidence ratios (SIRs) were calculated to compare rates in the areas near the gas compression site to expected rates based on overall US cancer rates. RESULTS: Total cancer mortality (RR=0.91, 95% CI 0.88 to 0.94) and incidence (RR=0.95, 95% CI 0.94 to 0.97) were reduced significantly in Champaign County versus the comparison counties. Similarly, a reduced rate of total cancer was observed in analyses by zip code (proximal to the former gas plant) when compared with either similar counties (RR=0.89, 95% CI 0.86 to 0.93) or national standardised rates of cancer (SIR=0.88, 95% CI 0.85 to 0.91). CONCLUSIONS: This historical cancer assessment did not find an increased risk of total cancer or specific cancer types in communities near a former manufactured gas plant site.

Association of low-level arsenic exposure in drinking water with cardiovascular disease: a systematic review and risk assessment.

The U.S. Environmental Protection Agency (EPA) is developing an integrated assessment of non-cancer and cancer risk assessment of inorganic arsenic (iAs). Cardiovascular disease (CVD) in association with iAs exposure has been examined in a number of studies and provides a basis for evaluating a reference dose (RfD) for assessing potential non-cancer health risks of arsenic exposure. In this systematic review of low-level iAs exposure (i.e., <100-150µg/L arsenic water concentration) and CVD in human populations, 13 cohort and case-control studies from the United States, Taiwan, Bangladesh, and China were identified and critically examined for evidence for derivation of a RfD. Eight cross-sectional and ecological studies from the United States were also examined for additional information. Prospective cohort data from Bangladesh provided the strongest evidence for determining the point of departure in establishing a candidate RfD based on a combined endpoint of mortality from "ischemic heart disease and other heart diseases." This study as well as the overall literature supported a no-observed-adverse-effect level of 100µg/L for arsenic in water, which was equivalent to an iAs dose of 0.009mg/kg-day (based on population-specific water consumption rates and dietary iAs intake). The study population was likely sensitive to arsenic toxicity because of nutritional deficiencies affecting arsenic methylation and one-carbon metabolism, as well as increasing CVD risk. Evidence is less clear on the interaction of CVD risk factors in the United States (e.g., diabetes, obesity, and hypertension) with arsenic at low doses. Potential uncertainty factors up to 3 resulted in a RfD for CVD in the range of 0.003-0.009mg/kg-day. Although caution should be exercised in extrapolating these results to the U.S. general population, these doses allow a margin of exposure that is 10-30 times the current RfD derived by EPA (based on skin lesions in Southwest Taiwan). These findings suggest that the current EPA RfD is protective of CVD.

Arsenic exposure and bladder cancer: quantitative assessment of studies in human populations to detect risks at low doses.

While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers.

A systematic review of multivitamin-multimineral use and cardiovascular disease and cancer incidence and total mortality.

Multivitamin-multimineral (MVM) supplements are the most frequently used dietary supplements in the United States, with one third or more of the population using at least one daily. However, the health-related implications of MVM use are unclear. Thus, we systematically reviewed and summarized the prospective studies of MVM supplementation and all-cause and cause-specific mortality, as well as cardiovascular disease (CVD) and cancer incidence, to critically evaluate the current evidence on this topic. We included studies of generally healthy adult populations that evaluated multivitamin (the most commonly used dietary supplement) and/or multimineral supplement use or simultaneous use of 3 or more vitamins and minerals. We did not evaluate individual supplements. A total of 12 cohort studies and 3 primary prevention randomized controlled trials met our inclusion criteria. The majority of the studies were conducted in the United States (n = 11), and the remaining were conducted in European countries (n = 3) and Japan (n = 1). Although between-study methodological variation was present, most relative risks hovered closely around or slightly below the null value. No clear patterns of associations by study country, gender, smoking status, or frequency of use were observed. Based upon the available scientific evidence to date, supplementation with MVMs does not appear to increase all-cause mortality, cancer incidence or mortality, or CVD incidence or mortality and may provide a modest protective benefit.

Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors.

BACKGROUND: Hepatic metastases develop in approximately 50% of colorectal cancer (CRC) cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs) and estimated the summary effect for seven prognostic factors. METHODS: Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted. RESULTS: Five- and 10-year survival ranged from 16% to 74% (median 38%) and 9% to 69% (median 26%), respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7-7.3) years. Meta-relative risks (95% confidence intervals) by prognostic factor were: node positive primary, 1.6 (1.5-1.7); carcinoembryonic antigen level, 1.9 (1.1-3.2); extrahepatic disease, 1.9 (1.5-2.4); poor tumor grade, 1.9 (1.3-2.7); positive margin, 2.0 (1.7-2.5); >1 liver metastases, 1.6 (1.4-1.8); and >3 cm tumor diameter, 1.5 (1.3-1.8). Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume. CONCLUSION: The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive relationship with survival, and certain prognostic factors may prove useful in determining optimal therapeutic options. Due to the increasing complexity of surgical interventions for CLM and the inclusion of patients with higher disease burdens, future studies should consider the potential for selection and referral bias on survival.

Ingested nitrate and nitrite and stomach cancer risk: an updated review.

Nitrite and nitrate are naturally occurring molecules in vegetables and also added to cured and processed meats to delay spoilage and pathogenic bacteria growth. Research over the past 15 years has led to a paradigm change in our ideas about health effects of both nitrite and nitrate. Whereas, historically nitrite and nitrate were considered harmful food additives and listed as probable human carcinogens under conditions where endogenous nitrosation could take place, they are now considered by some as indispensible nutrients essential for cardiovascular health by promoting nitric oxide (NO) production. We provide an update to the literature and knowledge base concerning their safety. Most nitrite and nitrate exposure comes from naturally occurring and endogenous sources and part of the cell signaling effects of NO involve nitrosation. Nitrosation must now be considered broadly in terms of both S- and N-nitrosated species, since S-nitrosation is kinetically favored. Protein S-nitrosation is a significant part of the role of NO in cellular signal transduction and is involved in critical aspects of cardiovascular health. A critical review of the animal toxicology literature of nitrite indicates that in the absence of co-administration of a carcinogenic nitrosamine precursor, there is no evidence for carcinogenesis. Newly published prospective epidemiological cohort studies indicate that there is no association between estimated intake of nitrite and nitrate in the diet and stomach cancer. This new and growing body of evidence calls for a reconsideration of nitrite and nitrate safety.

A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies.

OBJECTIVE: To systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent "weight-of-evidence" (WOE) methodological approach. METHODS: Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. The AHS evaluated pesticide applicators as well as dose-response associations for specific pesticide compounds, whereas the large majority of non-AHS evaluated applicators but did not analyze specific compounds or dose-response trends. This WOE assessment of 153 different pesticide-outcome pairs emphasized several key evidentiary features: existence of statistically significant relative risks, magnitude of observed associations, results from the most reliable exposure assessments, and evidence of convincing dose-response relationships (i.e., those monotonically increasing, with statistically significant trend tests). RESULTS: Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Deficits of colon or rectal cancer were observed across most studies of pesticide applicators. After applying the WOE methodology to the epidemiologic studies of specific pesticide compounds and colon or rectal cancer, a number of pesticide-outcome pairs were identified and evaluated further based on positive statistical associations. Of these, only two-aldicarb and colon cancer and imazethapyr and proximal colon cancer-appears to warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose-response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk. CONCLUSION: The available epidemiologic evidence does not support a causal relationship between occupation as a pesticide applicator or specific pesticide exposures and colon or rectal cancer.

Meta-analysis of prospective studies of red meat consumption and colorectal cancer.

The relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate. To estimate the summary association between red meat intake and CRC and to examine sources of heterogeneity, a meta-analysis of prospective studies was conducted. Thirty-four prospective studies of red meat and CRC were identified, of which 25 represented independent nonoverlapping study populations. Summary relative risk estimates (SRREs) for high versus low intake and dose-response relationships were calculated. In the high versus low intake meta-analysis, the SRRE was 1.12 (95% CI: 1.04-1.21) with significant heterogeneity (P=0.014). Summary associations were modified by tumor site and sex. The SRREs for colon cancer and rectal cancer were 1.11 (95% CI: 1.03-1.19) and 1.19 (95% CI: 0.97-1.46), respectively. The SRREs among men and women were 1.21 (95% CI: 1.04-1.42) and 1.01 (95% CI: 0.87-1.17), respectively. The available epidemiologic data are not sufficient to support an independent and unequivocal positive association between red meat intake and CRC. This conclusion is based on summary associations that are weak in magnitude, heterogeneity across studies, inconsistent patterns of associations across the subgroup analyses, and the likely influence of confounding by other dietary and lifestyle factors.