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.

A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.

OBJECTIVE: To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. METHODS: A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. RESULTS: Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. CONCLUSION: Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.

Meta-analysis of Egg Consumption and Risk of Coronary Heart Disease and Stroke.

The possible relationship between dietary cholesterol and cardiac outcomes has been scrutinized for decades. However, recent reviews of the literature have suggested that dietary cholesterol is not a nutrient of concern. Thus, we conducted a meta-analysis of egg intake (a significant contributor to dietary cholesterol) and risk of coronary heart disease (CHD) and stroke. A comprehensive literature search was conducted through August 2015 to identify prospective cohort studies that reported risk estimates for egg consumption in association with CHD or stroke. Random-effects meta-analysis was used to generate summary relative risk estimates (SRREs) for high vs low intake and stratified intake dose-response analyses. Heterogeneity was examined in subgroups where sensitivity and meta regression analyses were conducted based on increasing egg intake. A 12% decreased risk (SRRE = 0.88, 95% confidence interval [CI], 0.81-0.97) of stroke was observed in the meta-analysis of 7 studies of egg intake (high vs low; generally 1/d vs <2/wk), with little heterogeneity (p-H = 0.37, I2 = 7.50). A nonstatistically significant SRRE of 0.97 (95% CI, 0.88-1.07, p-H = 0.67, I2 = 0.00) was observed in the meta-analysis of 7 studies of egg consumption and CHD. No clear dose-response trends were apparent in the stratified intake meta-analyses or the meta regression analyses. Based on the results of this meta-analysis, consumption of up to one egg daily may contribute to a decreased risk of total stroke, and daily egg intake does not appear to be associated with risk of CHD. Key Teaching Points: • The role of egg consumption in the risk of stroke and coronary heart disease has come under scrutiny over many years. • A comprehensive meta-analysis of prospective cohort studies that reported risk estimates for egg consumption in association with CHD or stroke was performed on the peer-reviewed epidemiologic literature through August 2015. • Overall, summary associations indicate that intake of up to 1 egg daily may be associated with reduced risk of total stroke. • Overall, summary associations show no clear association between egg intake and increased or decreased risk of CHD. • Eggs are a relatively low-cost and nutrient-dense whole food that provides a valuable source of protein, essential fatty acids, antioxidants, choline, vitamins, and minerals.

Growth of infants consuming whey-predominant term infant formulas with a protein content of 1.8 g/100 kcal: a multicenter pooled analysis of individual participant data.

BACKGROUND: High protein intake during infancy may contribute to obesity later in life in infants who are not exclusively breastfed. Lowering the protein content of infant formula so it is closer to that of mature breast milk may reduce long-term risk of overweight or obesity in formula-fed infants. OBJECTIVE: We assessed the effects of whey-predominant formulas with a protein content of 1.8 g/100 kcal (lower than that in most current formulas and closer to breast milk) on infant growth by comparing against WHO growth standards and breastfed infants. DESIGN: A multicenter pooled analysis was conducted with the use of individual participant data (n = 1882) from 11 randomized controlled trials of healthy term infants. Mixed-effects models that used ANCOVA were generated to estimate weight-for-age z score (WAZ), as well as length-for-age, BMI-for-age, and head circumference-for-age z scores at age 4 mo in infants fed a lower-protein infant formula (LPF) or a lower-protein infant formula with additional active ingredients (probiotics, prebiotics, or both) (LPFA) and breastfed infants. Estimates, including 95% CIs, were compared with a ±0.5 SD of WHO growth standards, a benchmark for clinically significant differences. RESULTS: The 95% CIs for pooled estimates of WAZ were within ±0.5 SD of WHO growth standards for the LPF [0.07 (-0.16, 0.29)] and LPFA [0.22 (0.01, 0.43)] groups. WAZ was higher in the LPF (P < 0.001) and LPFA (P = 0.003) groups than in the breastfed infants, likely because breastfed infants had a relatively low WAZ [-0.23 (-0.51, 0.05)] compared with WHO growth standards. The 95% CIs for all other z scores in the LPF and LPFA groups were within ±0.5 SD of WHO growth standards, except for head circumference, for which the upper limit of the 95% CI slightly exceeded 0.5 SD. No difference was observed in any z scores between the LPF and LPFA groups. CONCLUSION: Whey-predominant infant formula with a lower protein content that more closely resembles that of breast milk supports healthy growth comparable to the WHO growth standards and close to breastfed infants.

Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia.

BACKGROUND: Cardiovascular outcomes trials of fibrates, niacin, or omega-3 fatty acids alone, or added to a statin, have not consistently demonstrated reduced risk, but larger, statistically significant clinical benefits have been reported in subgroups with elevated triglycerides (TG) and/or elevated TG plus low high-density lipoprotein cholesterol (HDL-C). OBJECTIVE: To perform a meta-analysis of the effects of therapies targeting TG and TG-rich lipoprotein cholesterol on cardiovascular disease event risk in subjects with elevated TG or elevated TG paired with low HDL-C. METHODS: Publications were identified using PubMed, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Internet Stroke Center. Random-effects meta-analysis models were used to generate summary relative risk estimates and 95% confidence intervals. Heterogeneity was assessed by χ(2) and I(2) statistics, and the impact of each trial was assessed in one study-removed sensitivity analyses. RESULTS: Six trials of fibrates, 2 of niacin, 1 of fibrate + niacin, and 1 of omega-3 eicosapentaenoic acid ethyl esters were identified. For the prespecified primary cardiovascular disease or coronary heart disease end point used in each trial, the summary relative risk estimate (95% confidence interval) for subjects with elevated TG was 0.82 (0.73-0.91), p-heterogeneity = 0.13, I(2) = 36.2, and for subjects with elevated TG and low-HDL-C, it was 0.71 (0.63-0.81), p-heterogeneity = 0.52, I(2) = 0.0. There was no evidence of publication bias, and the results remained statistically significant when each individual trial was removed. CONCLUSION: Drugs that substantially, but not exclusively, lower TG and TG-rich lipoprotein cholesterol may have cardiovascular benefits in individuals with elevated TG, particularly if accompanied by low HDL-C.

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.

Dairy consumption and CVD: a systematic review and meta-analysis.

Inverse associations between dairy consumption and CVD have been reported in several epidemiological studies. Our objective was to conduct a meta-analysis of prospective cohort studies of dairy intake and CVD. A comprehensive literature search was conducted to identify studies that reported risk estimates for total dairy intake, individual dairy products, low/full-fat dairy intake, Ca from dairy sources and CVD, CHD and stroke. Random-effects meta-analyses were used to generate summary relative risk estimates (SRRE) for high v. low intake and stratified intake dose-response analyses. Additional dose-response analyses were performed. Heterogeneity was examined in sub-group and sensitivity analyses. In total, thirty-one unique cohort studies were identified and included in the meta-analysis. Several statistically significant SRRE below 1.0 were observed, namely for total dairy intake and stroke (SRRE=0·91; 95% CI 0·83, 0·99), cheese intake and CHD (SRRE=0·82; 95% CI 0·72, 0·93) and stroke (SRRE=0·87; 95% CI 0·77, 0·99), and Ca from dairy sources and stroke (SRRE=0·69; 95% CI 0·60, 0·81). However, there was little evidence for inverse dose-response relationships between the dairy variables and CHD and stroke after adjusting for within-study covariance. The results of this meta-analysis of prospective cohort studies have shown that dairy consumption may be associated with reduced risks of CVD, although additional data are needed to more comprehensively examine potential dose-response patterns.

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.