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KSR Number: KSRA112062

Reduction of red and processed meat intake and cancer mortality and incidence: a systematic review and meta-analysis of cohort studies

Risk of Bias Assessment

Overall summary: Risk of bias unclear

Bottom Line

Evidence from observational studies shows that a reduction of three servings per week of red meat or processed meat may reduce the risk of death from cancer. There was also evidence for very small reductions in deaths from prostate cancer and incidence of oesophageal, colorectal and breast cancer with reductions in processed meat intake. However, the estimated lifetime effects of exposure are very small, the overall certainty of evidence is low or very low, and a causal relationship has not been established. There was a lack of information about other cancer risk factors and the results of each study. Some analyses had high statistical heterogeneity and the pooled results may not be reliable, as reflected by certainty of the evidence.

Risk of Bias Assessment

Overall summary Risk of bias unclear

Unclear

It was unclear why the review was restricted to studies of more than 1000 participants. Baseline study characteristics regarding cancer risk were not reported. Three different meta-analysis methods were used but the results and GRADE assessment were based on the dose-response analysis as this was considered to be the most reliable but no justification was provided. Some analyses had high statistical heterogeneity and the pooled results may not be reliable.

A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? Probably no
B. Was the relevance of identified studies to the review's research question appropriately considered? Probably yes
C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Probably yes
Risk of bias in the review Unclear

Details of Review

Number of studies 56
Number of participants > 6000000
Last search date April 2019
Review type Aetiological
Objective To evaluate the possible causal relationship between intake of red and processed meat and cancer incidence and mortality.
Population General adult (aged 18 years or older) population.

Studies were excluded if >20% of the sample was pregnant or had major chronic illness at baseline, including cancer, and where participants without these conditions were not reported separately.
Outcome Mortality from or incidence of any of the following: cancer overall, gastrointestinal cancer (oral, oesophageal, gastric, small intestinal, colorectal, hepatic, pancreatic, or gallbladder), female cancer types (ovarian, endometrial, or breast), or prostate cancer.
Study design Cohort studies with more than 1000 participants.
Reference standard NA
Exposure Consumption of 3 servings per week of red meat or processed meat.

Studies were excluded if they reported only consumption of a specific type of red meat (e.g. beef or lamb) or a specific type of processed meat (e.g. hot dogs).

Studies that asked participants to recall their diet at a previous point in their life (for example, if adults recalled their diet during adolescence and childhood or middle-aged adults recalled their diet during young adulthood) were also excluded.
PP factor Consumption of 3 servings per week of red meat or processed meat.

Studies were excluded if they reported only consumption of a specific type of red meat (e.g. beef or lamb) or a specific type of processed meat (e.g. hot dogs).

Studies that asked participants to recall their diet at a previous point in their life (for example, if adults recalled their diet during adolescence and childhood or middle-aged adults recalled their diet during young adulthood) were also excluded.

Results

Low certainty evidence indicated that a reduction in unprocessed red meat intake of three servings per week was associated with a very small decrease in overall cancer mortality (relative risk [RR] 0.93, 95% confidence interval [CI]: 0.91 to 0.94), 7 studies; 8 fewer cancer deaths per 1000 people). The results of analyses for overall cancer incidence and for incidence of individual cancer types (oesophageal, gastric, colorectal, pancreatic, breast and prostate) were not statistically significant and based on evidence of low or very low quality due to the observational design of the studies.

Low certainty evidence indicated that a reduction in processed meat intake of three servings per week was associated with a very small decrease in overall cancer mortality (RR 0.92, 95% CI: 0.89 to 0.94, 3 studies; 7 fewer cancer deaths per 1000 people). Similarly, very low certainty evidence indicated that a reduction in processed meat intake of three servings per week was associated with a small reduction in prostate cancer deaths (RR 0.77, 95% CI 0.66 to 0.90; 2 studies; 1 fewer death per 1000 people). Mortality results for other specific cancer types (gastric, colorectal and pancreatic) were uncertain and based on very low to low quality evidence.

A reduction in processed meat intake of three servings per week was also associated with small reductions in the incidence of some cancer types: breast (RR 0.90, 95% CI 0.85 to 0.95, 8 studies; 5 fewer deaths); oesophagal (RR 0.70, 95% CI 0.56 to 0.88, 1 study; 2 fewer deaths) and colorectal (RR 0.93, 95% CI 0.89 to 0.95. 15 studies; 1 fewer death). Results overall cancer incidence, and for incidence of individual cancer types (oral, gastric, small intestine, liver, pancreatic, ovarian, endometrial and prostate) were highly uncertain and and based on very low to low quality evidence.

Full Risk of Bias Assessment

The research objective was clearly stated. The reported inclusion criteria were broadly appropriate, however, the authors did not provide the reasoning for their choice of minimum sample size (n=1000) or for the decision to exclude studies that assessed the relationship between consumption of specific types of meat and cancer incidence and mortality. No language or publication status restrictions were applied.

1.1 Did the review adhere to pre-defined objectives and eligibility criteria? Yes
1.2 Were the eligibility criteria appropriate for the review question? Probably yes
1.3 Were eligibility criteria unambiguous? Yes
1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? No information
1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Probably yes
Concerns regarding specification of study eligibility criteria Unclear

MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CINAHL and ProQuest were searched from inception to July 2018 and update searches were undertaken (MEDLINE only) to April 2019. The reference lists of published systematic reviews were screened for additional articles. The search strategies used for each database were published in full (supplementary material) and appeared adequate. No date or language limitations were applied. Two reviewers independently assessed studies for inclusion and any disagreements were resolved through discussion or consultation with a third reviewer.

2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? Probably yes
2.2 Were methods additional to database searching used to identify relevant reports? Yes
2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? Probably yes
2.4 Were restrictions based on date, publication format, or language appropriate? Yes
2.5 Were efforts made to minimise error in selection of studies? Yes
Concerns regarding methods used to identify and/or select studies Low

Two reviewers independently extracted data from included studies, using a predefined data extraction form, and any disagreements were resolved through discussion or consultation with a third reviewer. The risk of bias of included studies was assessed using a modified version of the Clinical Advances through Research and Information Technology risk of bias tool. Risk of bias was assessed independently by two reviewers and any disagreements were resolved through discussion or consultation with a third reviewer; studies were considered to have high risk of bias if two or more of the seven items were classified as high risk after consensus. The criteria considered are relevant for aetiologic studies but do not provide a comprehensive assessment. Some details of the included studies (e.g. participant age at baseline, gender distribution, duration of follow-up) were reported as supplementary material, however, no information was provided about other potential cancer risk factors (e.g. family history, genetic markers, smoking, weight) although adjustment for other risk factors formed part of the risk of bias assessment.

3.1 Were efforts made to minimise error in data collection? Yes
3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results? Probably no
3.3 Were all relevant study results collected for use in the synthesis? Probably yes
3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? Probably yes
3.5 Were efforts made to minimise error in risk of bias assessment? Yes
Concerns regarding methods used to collect data and appraise studies Unclear

All studies appear to have been included in the synthesis. Dose-response meta-analysis was used to calculate pooled relative risks for the association of a reduction in 3 servings per week with cancer outcomes. If relevant data were not available then the quantity of meat intake and numbers of person-years were estimated. If analyses included 5 or more studies then the nonlinear association between meat intake and cancer risk was modelled using restricted cubic splines. Random effects meta-analysis was also used to compare the lowest and highest categories of meat intake. Statistical heterogeneity was measured using the I-squared statistic but clinical heterogeneity was not discussed. Meta-regression was used to investigate the impact of risk of bias on the summary estimates. Publication bias was evaluated using the Egger test. The results of the dose-response analyses were given priority but this decision was not justified. Individual study results were not presented.

4.1 Did the synthesis include all studies that it should? Probably yes
4.2 Were all pre-defined analyses reported or departures explained? Probably yes
4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies? Probably yes
4.4 Was between-study variation minimal or addressed in the synthesis? Probably no
4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? Probably yes
4.6 Were biases in primary studies minimal or addressed in the synthesis? Probably yes
Concerns regarding synthesis and findings Unclear

Abstract

Background: Cancer incidence has continuously increased over the past few centuries and represents a major health burden worldwide. Purpose: To evaluate the possible causal relationship between intake of red and processed meat and cancer mortality and incidence. Data Sources: Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019 without language restrictions. Study Selection: Cohort studies that included more than 1000 adults and reported the association between consumption of unprocessed red and processed meat and cancer mortality and incidence. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias; 1 reviewer evaluated the certainty of evidence, which was confirmed or revised by the senior reviewer. Data Synthesis: Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose–response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer. Limitation: Limited causal inferences due to residual confounding in observational studies, risk of bias due to limitations in diet assessment and adjustment for confounders, recall bias in dietary assessment, and insufficient data for planned subgroup analyses. Conclusion: The possible absolute effects of red and processed meat consumption on cancer mortality and incidence are very small, and the certainty of evidence is low to very low. Primary Funding Source: None. (PROSPERO: CRD42017074074)