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Oncology
Research
Dairy product consumption and development of cancer: an overview of reviews
  1. Maya M Jeyaraman1,2,
  2. Ahmed M Abou-Setta1,2,
  3. Laurel Grant3,
  4. Farnaz Farshidfar1,
  5. Leslie Copstein1,
  6. Justin Lys1,
  7. Tania Gottschalk4,
  8. Danielle Desautels3,5,6,
  9. Piotr Czaykowski2,3,5,6,
  10. Marshall Pitz2,3,5,6,7,
  11. Ryan Zarychanski1,2,3,5,6,7
  1. 1 The George & Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada
  2. 2 Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  3. 3 Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
  4. 4 Neil John Maclean Health Sciences Library, University of Manitoba, Winnipeg, Manitoba, Canada
  5. 5 Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
  6. 6 Department of Medical Oncology and Hematology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada
  7. 7 Research Institute in Oncology and Hematology, University of Manitoba and CancerCare Manitoba, Winnipeg, Manitoba, Canada
  1. Correspondence to Dr Maya M Jeyaraman; maya.jeyaraman{at}umanitoba.ca

Abstract

Objectives To provide a comprehensive systematic overview of current evidence from pooled analyses/meta-analyses and systematic reviews (PMASRs) pertaining to dairy consumption and incident cancer and/or all-cause or cancer-specific mortality.

Design Overview of reviews.

Setting Community setting.

Participants The unit of analysis is PMASRs. A total of 42 PMASRs was included in this overview of reviews.

Interventions/exposures Any dairy product consumption (eg, milk, yogurt, etc).

Primary and secondary outcomes measures Primary outcome measure is development of any type of cancer. Secondary outcome measures are all-cause mortality and cancer-specific mortality.

Results From 9693 citations identified, we included 42 PMASRs (52 study reports) published between 1991 and 2017. Thirty-one (74%) of these was pooled analyses/meta analyses, and only 11 (26%) were systematic reviews and meta-analyses. There was a wide variability in the type of study designs included within the other PMASRs, thus contributing to variable and, in instances, divergent estimates of cancer risk for several cancer subtypes. For example, only one systematic review and meta-analysis exclusively included prospective study designs. Most PMASRs were of low to moderate quality based on the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scores. The median AMSTAR score was 5 (IQR 2–7). Our overview identified conflicting evidence from PMASRs on association between dairy consumption and incident cancers or mortality. Heterogeneity in summary estimates reflected the inclusion of variable study designs and overall low methodological quality of individual PMASRs.

Conclusions The association between dairy consumption and cancer risk has been explored in PMASRs with a variety of study designs and of low to moderate quality. To fully characterise valid associations between dairy consumption and risk of cancer and/or mortality rigorously conducted, PMASRs including only high-quality prospective study designs are required.

Trial registration number CRD42017078463.

  • dairy
  • dairy products
  • cancer
  • overview of reviews

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2018-023625

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    Strengths and limitations of this study

    • To the best of our knowledge, this is the first overview of reviews to synthesise current evidence from pooled  analyses/meta-analyses   and systematic reviews (PMASRs) that evaluated associations between dairy consumption and development of incident cancer and/or mortality.

    • Comprehensive search strategy and a systematic review methodology.

    • An a priori protocol registered in Prospective Register of Systematic Reviews.

    • Only included English-language PMASRs.

    • Marked heterogeneity among included PMASRs with respect to study design and methodological quality of included studies limits ability to reach valid conclusions regarding associations or causal inferences.

    Introduction 

    Cancer is a major public health issue in North America and worldwide,1 with a global burden that is expected to grow to 21.7 million new cases and 13 million cancer deaths by 2030.2 3 Cancer is the leading cause of mortality in Canada (30.2%)4 and the second leading cause of mortality in the USA.1 Many risk factors such as genetic inheritance, diet, physical inactivity, smoking, alcohol consumption and exposure to environmental pollution and radiation have been associated with the development of cancer.5 Only 5%–10% of cancers are attributed to inherited genetic defects,5 while the remaining 90%–95% of all cancers are attributed to either environmental or lifestyle factors.5 A direct relationship between diet and an increased risk of cancer has been well described. It is estimated that diet accounts for 35% of all cancer risk.6

    Milk and dairy products from various animal sources are considered well-balanced nutritive foods,7 and dietary guidelines recommend a daily consumption of low-fat dairy products for optimal health.8 Recently, however, the assumed beneficial effects of dairy consumption have been questioned and potential risks have been identified by nutrition scientists9 and authors.10 11 While dairy products are believed to be rich in bioactive compounds that may be beneficial to health,7 12 studies have also suggested that dairy may contain harmful reproductive and cancer-causing hormones13 14 and that regular dairy consumption may promote cancer by increasing insulin-like growth factor levels.15 Several epidemiological studies have explored the association between dairy consumption and risk of various cancers but the evidence from primary research remains inconclusive and controversial.7 16–18

    Numerous pooled analyses/meta-analyses and systematic reviews (PMASRs) have synthesised a variety of data-exploring associations between dairy products consumption and cancer incidence.19–23 The scope, objectives, outcomes and the methodological quality of these PMASRs are diverse. In order to inform clinical decision-making and to guide future research, we conducted an overview of reviews to identify the totality of evidence currently available from PMASRs. Our objective is to provide a systematic and comprehensive critical appraisal of synthesised evidence evaluating the association of dairy consumption and incident cancer and all-cause or cancer-specific mortality.

    Methods

    We conducted this overview of reviews using an a priori protocol (CRD42017078463)24 (online supplementary file) and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).25 The eligibility criteria are reported in online supplementary table 1.

    Supplemental material

    Supplemental material

    Search methods

    We searched for PMASRs on dairy consumption and cancer using a peer-reviewed comprehensive search strategy of the following bibliographic databases: PubMed (National Library of Medicine), Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley), Centre for Agriculture and Biosciences (CAB) abstracts (Ovid), Food, Science & Technology (Ovid) and Cumulative Index to Nursing and Allied Health Literature (CIHAHL) (EbscoHost) from inception to July 2017, irrespective of the publication status or publication year. We also searched Web of Science-Science Citation Index (Clarivate Analytics), Web of Science-Conference Abstracts (Clarivate Analytics) and Scopus (Elsevier). To identify additional potentially relevant studies, we performed forward searches in Scopus (Elsevier) and Web of Science (Clarivate Analytics). We hand-searched conference proceedings (2014–2017) for the following conferences: American Society of Clinical Oncology’s annual meeting (ASCO), American Association for Cancer Research (AACR) Annual Meeting, and European Society for Medical Oncology (ESMO). We contacted experts in the field and searched Prospective Register of Systematic Reviews (PROSPERO) for relevant unpublished reviews. We used EndNote (V.X7, Thomson Reuters) for reference management. Our search strategy for Medline is reported in online supplementary table 2. We used the study design filter for systematic reviews and meta-analysis in our search strategies formatted for the various databases.

    Study selection process

    Two reviewers (MJ and one of LG, JL or AS) independently screened the titles and abstracts of citations identified by our search strategy. Each screened abstract was marked as either, included, excluded or unsure. Conflicts were resolved using consensus or third-party adjudication. Full texts were retrieved for the citations marked as either included or unsure. Full-text screening was performed by two reviewers (LG and either FF or LC) and conflicts were again resolved either through consensus or third-party adjudication. A PRISMA flow diagram illustrating the number of studies either included or excluded at each step of the study selection process is reported in figure 1.

    Figure 1
    Figure 1

    Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram depicting study selection process.

    Dealing with companion publications

    In the event of companion reports of an included PMASR, we used the publication that contained the most complete information relevant to our overview of reviews as the primary report and listed all other companion publications as secondary reports under the primary reference of the included PMASR.

    Assessment of methodological quality of included reviews

    We used the Assessing the Methodological Quality of Systematic Reviews (AMSTAR)26 tool to assess the methodological quality/internal validity of each of the included PMASRs. Two reviewers (LG and either of FF or LC) independently assessed the quality of the included PMASRs and resolved conflicts either through consensus or third party adjudication (figure 2).

    Figure 2
    Figure 2

    Bar chart depicting the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scores of included pooled  analyses/meta-analyses   and systematic reviews  (PMASRs). The y-axis represents the percentage of included PMASRs, and the x-axis represents the AMSTAR scores (low, moderate or high).

    Data extraction and analysis

    We developed, piloted and used customised data extraction forms to extract data from included PMASRs. Two review authors (LG and either of FF or LC) independently extracted the characteristics and the summary effect estimates and CIs with conflicts resolved through consensus or third-party adjudication. The individual study characteristics extracted from the included PMASRs are itemised in table 1 and online supplementary table 3. We analysed the extracted study characteristics using Microsoft Excel (Excel V. 14, Microsoft, Redmond, Washington, USA). Categorical and continuous data from included PMASRs are reported as proportions or medians/means with accompanying measures of variance where appropriate. The summary effect estimates from 156 meta-analyses (comparing highest vs lowest dairy intake) reported by the included PMASRs were extracted and are reported in online supplementary tables 4, 5 and 6. We assessed the nature of association for each of the meta-analysis reported in the PMASRs based on the extracted summary effect estimates and the CIs.

    View this table:
    Table 1

    Key features of the included pooled  analyses/meta-analyses   and systematic reviews (PMASRs)

    The number of studies reporting the nature of association between dairy consumption and each type of cancer outcome has been reported using radar plot in figure 3. The number of studies reporting the nature of association between various dairy products and specific gastrointestinal or hormone dependent cancer is reported using radar plot in figures 4 and 5.

    Figure 3
    Figure 3

    Radar plot depicting the nature of association between dairy consumption and risk of cancer (as reported in included pooled   analyses / meta- analyses    and systematic reviews (PMASRs)). The numbers on the plot represent the total number of meta-analyses from included PMASRs reporting a specific cancer association. The black, red, and green lines represent number of meta-analyses reporting no association with, increased risk or decreased risk of specific type of cancer, respectively.

    Figure 4
    Figure 4

    Radar plots depicting the associations between various dairy products consumption and risk of gastrointestinal cancer. The numbers on the circles of each plot represent the total number of meta-analyses from included pooled   analyses / meta- analyses    and systematic reviews reporting a specific cancer association. The black and green lines represent number of meta-analyses reporting no association with or decreased risk of gastrointestinal cancers, respectively.

    Patient involvement

    Patients were not involved in this overview of reviews.

    Results

    Search results

    We identified 9693 unique records from searching electronic databases and 3 additional records through hand-searching; 42 PMASRs (52 reports) met our inclusion criteria and were included in this overview of reviews (figure 1).

    Description of included PMASRs

    The included PMASRs were published between 1991 and 2017. In total, 31 (74%) were pooled analyses/meta-analyses and 11 (26%) were systematic reviews and meta-analyses. The 1119 20 27–35 systematic reviews and meta-analysis reported on the risks of colorectal cancer,27 31 33 prostate cancer,20 lung cancer,19 breast cancer,28 35 gastric cancer,32 34 ovarian cancer29 or oesophageal cancer.30 One systematic review33 was included as three separate PMASRs because the data were reported separately for three different patient populations based on their ability to digest lactose. The PMASRs included many study designs such as cohort, case–control, nested-case–control and case-cohorts (online supplementary table 3). Only 1 (2%) of the 11 systematic reviews and meta-analysis exclusively included prospective cohort studies. The PMASRs included primary studies that were conducted in various continents (online supplementary table 3). The number (%) of PMASRs that included primary studies from different continents is as follows: Europe (n=39 (93%)), North America (n=35 (83%)), Asia (n=27 (64%)), South America (n=13 (31%)) or Oceania (n=9 (21%)). Most PMASRs (n=26 (62%)) were funded by non-industry sources; few (n=2 (5%)) were industry sponsored and the remaining (n=14 (33%)) did not report a source of funding. Informative subgroup analyses, evaluation of publication bias and meta-regression based on important potential confounders were performed in 62%, 55% and 33% of PMASRs, respectively. Most of the PMASRs reported using random-effects model (60%) for their analyses; 7% used fixed-effects models and 19% reported using both models. The key features and the individual characteristics of the included PMASRs are summarised in table 1 and online supplementary table 3.

    Methodological quality of included reviews

    The AMSTAR scores ranged from 1 to 8 out of a possible maximum score of 11. The median score and the IQR were 5 and (2.25–6.75), respectively. Thirty-eight per cent (16/42) of the PMASRs had a score of 1–3 (low quality), and 55% (23/42) had a score of 4–7 (moderate quality). Only 7% (3/42) of PMASRs had a high score of 8 (high quality), with none reaching the maximum score of 11 (figure 2 and online supplementary table 7). The 11 included systematic reviews and meta-analyses were mostly of moderate quality19 20 27–35 with 2 that were low35 and high quality.33 The domains of the AMSTAR tool in which most PMASRs scored the lowest were for search of ‘grey literature’ or ‘unpublished literature’, providing a list of included and excluded studies, and providing source of funding for each of the included primary studies in the PMASR. The domains of the AMSTAR tool in which most PMASRs scored the highest were for providing characteristics of included studies and using appropriate methods for pooling data from primary studies. The relationship between AMSTAR scores and the publication year of the included PMASRs is reported using a line plot in online supplementary figure 1.

    Primary outcome

    Nature of association between dairy consumption and risk of cancer

    The various dairy products (n=19) reported as exposures in the PMASRs were all-dairy products, whole milk, milk, fermented milk, non-fermented milk, low-fat milk, skim-milk, yogurt, cheese, hard cheese, cottage cheese, butter, solid cheese, dairy calcium, ice cream, fermented dairy, low-fat dairy, high-fat dairy and lactose. We grouped the reported cancer outcomes (n=14) in the PMASRs into gastrointestinal cancers (oesophageal, gastric, pancreatic and colorectal cancers); hormone-dependent cancers (prostate, ovarian, endometrial and breast cancers); other cancers (bladder cancer, renal cell cancer, lung cancer, thyroid cancer, non-Hodgkin’s lymphoma and multiple myeloma).

    Out of 153 reported meta-analyses (comparing highest vs lowest dairy consumption) in the 42 PMASRs, 109 (71%) showed no evidence of a statistically significant association between dairy consumption and incidence of cancers, 20 (13%) showed decreased risk of cancers with dairy consumption and 24 (16%) showed increased risk of cancers with dairy consumption. The nature of associations between various dairy product exposures and the risk of cancer is depicted in table 2 and figure 3.

    View this table:
    Table 2

    Nature of association between dairy consumption and risk of cancer reported in included pooled  analyses / meta-  analyses and systematic reviews

    Nature of association between dairy consumption and gastrointestinal cancers

    The nature of association between various dairy exposures and the risk of gastrointestinal cancers is depicted in figure 4. Out of 14 cancer outcomes reported in the included PMASRs, the following 4 were gastrointestinal cancers.

    Oesophageal cancer

    Six meta-analyses30 36 explored associations between various dairy products consumption and risk of oesophageal cancer. Four meta-analyses30 showed non-significant associations between ‘all-dairy products’, milk, cheese or butter consumption and risk of oesophageal cancer. Two meta-analyses30 36 showed decreased risk of oesophageal cancer with higher yogurt or ‘all-dairy products’ consumption.

    Gastric cancer

    A total of 11 meta-analyses32 34 37 38 explored associations between dairy consumption and risk of gastric cancer. Ten32 34 37 showed non-significant associations between ‘all-dairy products’, milk, yogurt, cheese or butter consumption and risk of gastric cancer. One38 meta-analysis showed decreased risk of gastric cancer with higher milk consumption.

    Pancreatic cancer

    Eight meta-analyses23 39 showed non-significant associations between whole milk, milk, low-fat milk, skim milk, yogurt, cheese, cottage cheese or ice cream consumption and risk of pancreatic cancer. None of the dairy products was shown to either decrease or increase the risk of pancreatic cancer.

    Colorectal cancer

    Twenty-nine meta-analyses27 31 33 40–43 explored associations between various dairy products and risk of colorectal cancer. Twenty meta-analyses27 31 33 40–43 showed non-significant associations between ‘all-dairy products’, milk, fermented milk, yogurt, cheese, cottage cheese, butter, solid cheese, fermented dairy, low-fat dairy or high-fat dairy consumption and risk of colorectal cancer. Nine meta-analyses27 31 33 40 43 showed decreased risk of colorectal cancer with higher consumption of milk, non-fermented milk or ‘all-dairy products’.

    Evidence from systematic reviews and meta-analysis

    Evidence from available systematic reviews and meta-analyses on oesophageal,30 gastric32 34 or colorectal cancer27 31 33 showed either a non-significant association or decreased risk with higher dairy products intake (table 3 and online supplementary table 8).

    View this table:
    Table 3

    Nature of association between dairy consumption and risk of cancer: evidence from systematic reviews and meta-analysis

    Nature of association between dairy consumption and hormone-dependent cancers

    The nature of associations between various dairy exposures and the risk of hormone-dependent cancers is depicted in figure 5. Out of 14 cancer outcomes reported in the included PMASRs, the following 4 were hormone-dependent cancers.

    Figure 5
    Figure 5

    Radar plots depicting the nature of association between various dairy products consumption and risk of hormone-dependent cancers. The numbers on the circles of each plot represent the total number of meta-analyses from included pooled  analyses/meta- analyses and systematic reviews reporting a specific cancer association. The black, red and green lines represent number of meta-analyses reporting no association with, increased risk or decreased risk of hormone-dependent cancers, respectively.

    Prostate cancer

    Twenty-eight meta-analyses20 44–49 explored associations between various dairy products consumption and risk of prostate cancer. Thirteen meta-analyses20 44–46 49 showed non-significant association between ‘all-dairy products’, milk, skim milk, yogurt, cheese, butter or ice cream consumption and risk of prostate cancer. Two meta-analyses20 44 showed decreased risk of prostate cancer with higher whole milk and cheese consumption. Thirteen meta-analyses20 44 45 47 48 showed increased risk of prostate cancer with higher consumption of ‘all-dairy products’, milk, low-fat milk, cheese or dairy calcium.

    Ovarian cancer

    A total of 29 meta-analyses29 50–53 explored associations between various dairy products consumption and risk of ovarian cancer. Twenty-six meta-analyses29 50–53 showed non-significant associations between ‘all-dairy products’, whole milk, milk, low-fat milk, skim milk, yogurt, cheese, hard cheese, cottage cheese, butter, ice cream or lactose, consumption and risk of ovarian cancer. Three meta-analyses50 52 53 showed increased risk of ovarian cancer with higher consumption of whole milk or lactose exposure.

    Endometrial cancer

    Only one meta-analysis54 explored the association between ‘all-dairy products’ consumption and risk of endometrial cancer. ‘All-dairy products’ consumption was shown to increase the risk of endometrial cancer in this meta-analysis.

    Breast cancer

    Thirteen meta-analyses28 35 55 56 explored associations between various dairy products and risk of breast cancer. Eight meta-analyses28 35 55 showed non-significant associations between ‘all-dairy products’, whole milk, milk, low-fat milk, cheese, dairy calcium or high-fat dairy consumption and the risk of breast cancer. Three meta-analyses35 showed decreased risk of breast cancer with higher consumption of ‘all-dairy products’, yogurt or low-fat dairy. Two meta-analyses56 showed increased risk of breast cancer with higher consumption of milk or cheese.

    Evidence from systematic reviews and meta-analysis

    Evidence from systematic reviews and meta-analysis on prostate cancer,20 breast cancer28 35 or ovarian cancer29 indicates heterogeneous estimates of cancer risk pertaining to dairy consumption (table 3 and online supplementary table 8).

    Nature of association between dairy consumption and other reported cancers

    Bladder cancer

    Nine meta-analyses57 58 explored associations between various dairy products and risk of bladder cancer. Five meta-analyses57 58 showed non-significant associations between ‘all-dairy products’, milk, cheese or butter consumption and risk of bladder cancer. Three meta-analyses58 showed decreased risk of bladder cancer with higher consumption of milk, fermented milk or skim milk. One meta-analysis58 showed increased risk of bladder cancer with higher consumption of whole milk.

    Renal cell carcinoma

    Only one meta-analysis59 explored the association between milk consumption and risk of renal cell carcinoma. Milk consumption was non-significantly associated with risk of renal cell carcinoma in this meta-analysis.

    Lung cancer

    Seven meta-analyses19 60 explored associations between dairy products and risk of lung cancer. All seven meta-analyses showed non-significant associations between ‘all-dairy products’, milk, low-fat milk, yogurt or cheese consumption and risk of lung cancer.

    Non-Hodgkin’s lymphoma

    Nine meta-analyses61 62 explored associations between various dairy products and risk of non-Hodgkin’s lymphoma. Five meta-analyses61 62 showed non-significant associations between ‘all-dairy products’, milk, yogurt or cheese consumption and risk of non-Hodgkin’s lymphoma. Four meta-analyses62 showed increased risk of non-Hodgkin’s lymphoma with consumption of ‘all-dairy products’, milk, butter or ice cream.

    Multiple myeloma

    Two meta-analyses61 explored associations between milk or cheese consumption and risk of multiple myeloma and showed non-significant associations.

    Thyroid cancer

    Only one PMASR63 explored three associations between milk, cheese or butter and risk of thyroid cancer. Because CIs for the summary effect estimates were not reported, the nature of these associations was not assessable.

    Evidence from systematic reviews and meta-analysis

    One systematic review on lung cancer19 showed non-significant association between dairy consumption and lung cancer risk.

    Secondary outcomes

    Nature of association between dairy consumption and the risk of mortality

    All-cause mortality

    Only one PMASR64 reported meta-analyses exploring associations between ‘all-dairy products’, milk, cheese or butter consumption and risk of all-cause mortality (online supplementary table 8). Non-significant associations were found between ‘all-dairy products’, milk, cheese or butter consumption and risk of all-cause mortality.

    Cancer-specific mortality

    Three PMASRs19 64 65 reported non-significant association between milk consumption and cancer-specific mortality (online supplementary table 8). Two PMASRs64 65 reported non-significant association between yogurt, milk, cheese, all-dairy products or butter consumption and risk of cancer-specific mortality. One PMASR19 reported a significant decrease in risk of lung cancer-specific mortality with higher consumption of cheese and a non-significant association between milk consumption and lung cancer mortality.

    Discussion

    In this overview of reviews, we have provided an up-to-date comprehensive critical appraisal of 42 PMASRs (52 reports) that synthesised evidence on dairy consumption and risk of cancer. The current analyses revealed discrepant associations between dairy product consumption and risk of cancer when comparing highest versus the lowest levels of dairy consumption. None of the included primary studies in the PMASRs were randomised controlled trials (RCTs); thus we are only able to infer associations and not causality. In the context of variable and often discordant PMASRs, our study suggests that higher consumption of dairy products may be associated with decreased risk of gastrointestinal cancer and an uncertain or no established cancer risk associated with hormone-dependent or other hormone-independent cancers. Limited data precluded our ability to evaluate the association of dairy consumption on either all-cause mortality or cancer-specific mortality.

    Discussion of discrepant results

    Data suggested an inconsistent but perhaps increased risk of some hormone-dependent cancers with higher dairy consumption, but also suggested some conflicting associations for breast and prostate cancer. Exogenous oestrogens from milk products consumed today66 67 may explain the potential increased risk in hormone-dependent cancers. The evidence pertaining to hormone-dependent cancers reported in this overview was synthesised mostly by meta-analyses performed on diverse study types (including case reports, uncontrolled cohort studies and controlled cohort studies, either retrospective or prospective) of generally low to moderate methodological quality and thus could explain the conflicting associations reported. In contrast to the hormone-dependent cancers, data suggested an inconsistent but perhaps decreased risk of gastrointestinal cancers with higher dairy consumption. In many parts of the world, dairy products consumed today are fortified with vitamin D68 and also are a rich source of calcium, conjugated linoleic acid and sphingolipids.41 Studies have suggested that high intake of dietary calcium and vitamin D binds to free fatty acids and secondary bile acids in the digestive tract, reducing their toxic effects on gut epithelial cells and inhibiting proliferation of intestinal mucosa and epithelial cells.40 Thus the presence of these protective factors in dairy products may contribute to the decreased risk of gastrointestinal cancers associated with higher dairy consumption. Evidence report69 70 based on systematic literature review by the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) reported that higher consumption of dairy products might increase risk of prostate cancer and decrease the risk of premenopausal breast cancer (limited evidence), whereas dairy products might decrease the risk of colorectal cancer (strong but probable evidence).69 70 These findings are in agreement with the conclusions of our overview of reviews for the above three cancers. In addition, in our study we have also provided evidence for the association between dairy intake and other types of cancers not addressed by the WCRF/AICR report.

    Comparisons between ‘no dairy consumption’ and ‘high/low dairy consumption’ (compared with low dairy vs high dairy) may have more clearly defined the association between dairy intake and risks of hormone-dependent and gastrointestinal cancers as it is possible that the levels of reproductive hormones or protective factors in the dairy products may not have been sufficiently different between study populations consuming low dairy versus high dairy to see a significant impact of dairy on risk of cancer.

    Issues of representativeness

    In this overview, among the 11 included systematic review and meta-analyses, only one20 provided evidence exclusively from prospective study designs. It is important for systematic reviews and meta-analysis to derive evidence from prospective study designs such as RCTs or prospective controlled cohort studies in order to make any inference on causal association. Thus, high-quality evidence from systematic reviews of prospective study designs at low risk of bias is needed to assess the risk of cancers associated with high dairy consumption.

    Issues of mortality

    The evidence of no clear association between dairy product consumption and all-cause mortality comes from one PMASR.64 Similarly, evidence for dairy consumption and cancer-specific mortality comes from only three PMASRs and requires further study. In one PMASR19 reporting significant reduction in lung cancer-specific mortality, evidence was only from three primary studies (n=42 011 participants) reflecting a paucity of available data. Further primary studies and the completion of comprehensive high-quality systematic reviews are needed to explore the association between dairy consumption and risk of all-cause or cancer-specific mortality.

    Strengths and limitations

    This overview of reviews is the first to synthesise current evidence from PMASRs that evaluated associations between dairy consumption and risk of cancer and/or mortality. Our systematic review methods were comprehensive and our scientific protocol was established a priori and registered in PROSPERO.24 We included reviews of any date and type to provide an expansive summary of evidence on the topic. Our overview also has limitations. We only included English-language PMASRs. This may contribute to language bias and thus publication bias. The majority (12/14) of the excluded non-English citations did not appear to be PMASRs. As with any non-primary research, the results of this overview need to be interpreted with caution due to issues of heterogeneity. It is also important to recognise the overlap of the primary studies included in the PMASRs, the marked heterogeneity among included PMASRs with respect to included effect estimates and quality, and the predominantly retrospective nature of primary studies included in the PMASRs.

    Conclusions

    The association between dairy consumption and cancer risk has been explored with a variety of study designs in PMASRs of low to moderate quality. Limitations in the currently published PMASRs reduce the validity of previously published associations and mitigate assessment of causal association. To fully characterise valid associations between dairy consumption and risk of and/or cancer-related mortality, rigorously conducted systematic reviews and meta-analysis including only high-quality prospective study designs are required.

    Acknowledgments

    The authors thank Christine Nielson for help with running search strategies in various databases to identify relevant studies and Amrinder Singh Mann for help with screening.

    References

    1. 1.↵
      2. Siegel RL ,
      3. Miller KD ,
      4. Jemal A
      . Cancer statistics, 2017. CA Cancer J Clin 2017;67:7–30.doi:10.3322/caac.21387
      OpenUrlCrossRefPubMed
    2. 2.↵
      2. Ferlay J ,
      3. Soerjomataram I ,
      4. Dikshit R , et al
      . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–86.doi:10.1002/ijc.29210
      OpenUrlCrossRefPubMedWeb of Science
    3. 3.↵
      American Cancer Society. Global cancer facts and figures. 3rd edn. https://www.cancer.org/research/cancer-facts-statistics/global.html.
    4. 4.↵
      Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian cancer statistics 2017. Toronto, ON: Canadian Cancer Society, 2017. Available at. cancer.ca/Canadian-Cancer-Statistics-2017-EN.pdf. (accessed Jul 2017).
    5. 5.↵
      2. Anand P ,
      3. Kunnumakkara AB ,
      4. Kunnumakara AB , et al
      . Cancer is a preventable disease that requires major lifestyle changes. Pharm Res 2008;25:2097–116.doi:10.1007/s11095-008-9661-9
      OpenUrlCrossRefPubMedWeb of Science
    6. 6.↵
      2. Baena Ruiz R ,
      3. Salinas Hernández P
      . Diet and cancer: risk factors and epidemiological evidence. Maturitas 2014;77:202–8.doi:10.1016/j.maturitas.2013.11.010
      OpenUrlCrossRefPubMed
    7. 7.↵
      2. Pereira PC
      . Milk nutritional composition and its role in human health. Nutrition 2014;30:619–27.doi:10.1016/j.nut.2013.10.011
      OpenUrlCrossRefPubMed
    8. 8.↵
      U.S. Department of Health and Human Services and U.S, Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. 2015. Available at http://health.gov/dietaryguidelines/2015/guidelines/
    9. 9.↵
      2. Ludwig DS ,
      3. Willett WC
      . Three daily servings of reduced-fat milk: an evidence-based recommendation? JAMA Pediatr 2013;167:788–9.doi:10.1001/jamapediatrics.2013.2408
      OpenUrl
    10. 10.↵
    11. 11.↵
      2. Hyman M
      . Got proof? Lack of evidence for milk’s benefits. http://drhyman.com/blog/2013/07/05/got-proof-lack-of-evidence-for-milks-benefits/
    12. 12.↵
      2. Pufulete M
      . Intake of dairy products and risk of colorectal neoplasia. Nutr Res Rev 2008;21:56–67.doi:10.1017/S0954422408035920
      OpenUrlPubMedWeb of Science
    13. 13.↵
      2. Qin LQ ,
      3. Wang PY ,
      4. Kaneko T , et al
      . Estrogen: one of the risk factors in milk for prostate cancer. Med Hypotheses 2004;62:133–42.doi:10.1016/S0306-9877(03)00295-0
      OpenUrlCrossRefPubMedWeb of Science
    14. 14.↵
      2. Maruyama K ,
      3. Oshima T ,
      4. Ohyama K
      . Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows. Pediatr Int 2010;52:33–8.doi:10.1111/j.1442-200X.2009.02890.x
      OpenUrlCrossRefPubMed
    15. 15.↵
      2. Renehan AG ,
      3. Zwahlen M ,
      4. Minder C , et al
      . Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004;363:1346–53.doi:10.1016/S0140-6736(04)16044-3
      OpenUrlCrossRefPubMedWeb of Science
    16. 16.↵
      2. Thorning TK ,
      3. Raben A ,
      4. Tholstrup T , et al
      . Milk and dairy products: good or bad for human health? An assessment of the totality of scientific evidence. Food Nutr Res 2016;60:32527.doi:10.3402/fnr.v60.32527
      OpenUrl
    17. 17.↵
      2. Shin MH ,
      3. Holmes MD ,
      4. Hankinson SE , et al
      . Intake of dairy products, calcium, and vitamin d and risk of breast cancer. J Natl Cancer Inst 2002;94:1301–10.doi:10.1093/jnci/94.17.1301
      OpenUrlCrossRefPubMedWeb of Science
    18. 18.↵
      2. Farvid MS ,
      3. Malekshah AF ,
      4. Pourshams A , et al
      . Dairy food intake and all-cause, cardiovascular disease, and cancer mortality. Am J Epidemiol 2017;185:697–711.doi:10.1093/aje/kww139
      OpenUrl
    19. 19.↵
      2. Yang Y ,
      3. Wang X ,
      4. Yao Q , et al
      . Dairy product, calcium intake and lung cancer risk: a systematic review with meta-analysis. Sci Rep 2016;6:20624.doi:10.1038/srep20624
      OpenUrl
    20. 20.↵
      2. Aune D ,
      3. Navarro Rosenblatt DA ,
      4. Chan DS , et al
      . Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr 2015;101:87–117.doi:10.3945/ajcn.113.067157
      OpenUrlAbstract/FREE Full Text
    21. 21.↵
      2. Gao X ,
      3. LaValley MP ,
      4. Tucker KL
      . Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. JNCI: Journal of the National Cancer Institute 2005;97:1768–77.doi:10.1093/jnci/dji402
      OpenUrlCrossRefPubMedWeb of Science
    22. 22.↵
      2. Wang J ,
      3. Li X ,
      4. Zhang D
      . Dairy Product Consumption and Risk of Non-Hodgkin Lymphoma: A Meta-Analysis. Nutrients 2016;8:120.doi:10.3390/nu8030120
    23. 23.↵
      2. Genkinger JM ,
      3. Wang M ,
      4. Li R , et al
      . Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies. Ann Oncol 2014;25:1106–15.doi:10.1093/annonc/mdu019
      OpenUrlCrossRefPubMed
    24. 24.↵
      2. Jeyaraman MM ,
      3. Abou-Setta AM ,
      4. Grant L , et al
      . Dairy product consumption and risk of cancer – an overview of reviews. International Prospective Register of Systematic Reviews (PROSPERO). 2017 https://wwwcrdyorkacuk/prospero/display_recordphp?RecordID=78463.
    25. 25.↵
      2. Liberati A ,
      3. Altman DG ,
      4. Tetzlaff J , et al
      . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009;6:e1000100.doi:10.1371/journal.pmed.1000100
      OpenUrlCrossRefPubMed
    26. 26.↵
      2. Shea BJ ,
      3. Hamel C ,
      4. Wells GA , et al
      . AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. J Clin Epidemiol 2009;62:1013–20.doi:10.1016/j.jclinepi.2008.10.009
      OpenUrlCrossRefPubMedWeb of Science
    27. 27.↵
      2. Aune D ,
      3. Lau R ,
      4. Chan DS , et al
      . Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Ann Oncol 2012;23:37–45.doi:10.1093/annonc/mdr269
      OpenUrlCrossRefPubMed
    28. 28.↵
      2. Hidayat K ,
      3. Chen GC ,
      4. Zhang R , et al
      . Calcium intake and breast cancer risk: meta-analysis of prospective cohort studies. Br J Nutr 2016;116:158–66.doi:10.1017/S0007114516001768
      OpenUrl
    29. 29.↵
      2. Hou R ,
      3. Wu QJ ,
      4. Gong TT , et al
      . Dietary fat and fatty acid intake and epithelial ovarian cancer risk: evidence from epidemiological studies. Oncotarget 2015;6:43099–119.doi:10.18632/oncotarget.5525
      OpenUrl
    30. 30.↵
      2. Li BL ,
      3. Jiang GX ,
      4. Xue Q , et al
      . Dairy consumption and risk of esophageal squamous cell carcinoma: a meta-analysis of observational studies. Asia Pac J Clin Oncol 2016;12.doi:10.1111/ajco.12183
    31. 31.↵
      2. Ralston RA ,
      3. Truby H ,
      4. Palermo CE , et al
      . Colorectal cancer and nonfermented milk, solid cheese, and fermented milk consumption: a systematic review and meta-analysis of prospective studies. Crit Rev Food Sci Nutr 2014;54:1167–79.doi:10.1080/10408398.2011.629353
      OpenUrl
    32. 32.↵
      2. Sun Y ,
      3. Lin LJ ,
      4. Sang LX , et al
      . Dairy product consumption and gastric cancer risk: a meta-analysis. World J Gastroenterol 2014;20:15879–98.doi:10.3748/wjg.v20.i42.15879
      OpenUrl
    33. 33.↵
      2. Szilagyi A ,
      3. Nathwani U ,
      4. Vinokuroff C , et al
      . The effect of lactose maldigestion on the relationship between dairy food intake and colorectal cancer: a systematic review. Nutr Cancer 2006;55:141–50.doi:10.1207/s15327914nc5502_4
      OpenUrlPubMed
    34. 34.↵
      2. Tian SB ,
      3. Yu JC ,
      4. Kang WM , et al
      . Association between dairy intake and gastric cancer: a meta-analysis of observational studies. PLoS One 2014;9:e101728.doi:10.1371/journal.pone.0101728
    35. 35.↵
      2. Zang J ,
      3. Shen M ,
      4. Du S , et al
      . The association between dairy intake and breast cancer in western and asian populations: a systematic review and meta-analysis. J Breast Cancer 2015;18:313–22.doi:10.4048/jbc.2015.18.4.313
      OpenUrl
    36. 36.↵
      2. Li Q ,
      3. Cui L ,
      4. Tian Y , et al
      . Protective effect of dietary calcium intake on esophageal cancer risk: a meta-analysis of observational studies. Nutrients 2017;9:18.
    37. 37.↵
      2. Guo Y ,
      3. Shan Z ,
      4. Ren H , et al
      . Dairy consumption and gastric cancer risk: a meta-analysis of epidemiological studies. Nutr Cancer 2015;67:555–68.doi:10.1080/01635581.2015.1019634
      OpenUrl
    38. 38.↵
      2. N-y X ,
      3. J-h Z ,
      4. X-b Z , et al
      . Association between dietary factors and stomach cancer among Chinese people: A meta analysis. Bio Medical Information Engineering 2009:179.
    39. 39.↵
      2. Skinner HG ,
      3. Michaud DS ,
      4. Giovannucci E , et al
      . Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev 2006;15:1688–95.doi:10.1158/1055-9965.EPI-06-0206
      OpenUrlAbstract/FREE Full Text
    40. 40.↵
      2. Huncharek M ,
      3. Muscat J ,
      4. Kupelnick B
      . Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta-analysis of 26,335 cases from 60 observational studies. Nutr Cancer 2009;61:47–69.doi:10.1080/01635580802395733
      OpenUrlCrossRefPubMedWeb of Science
    41. 41.↵
      2. Norat T ,
      3. Riboli E
      . Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence. Eur J Clin Nutr 2003;57:1–17.doi:10.1038/sj.ejcn.1601522
      OpenUrlCrossRefPubMedWeb of Science
    42. 42.↵
      2. Rosato V ,
      3. Guercio V ,
      4. Bosetti C , et al
      . Mediterranean diet and colorectal cancer risk: a pooled analysis of three Italian case-control studies. Br J Cancer 2016;115:862–5.doi:10.1038/bjc.2016.245
      OpenUrl
    43. 43.↵
      2. Cho E ,
      3. Smith-Warner SA ,
      4. Spiegelman D , et al
      . Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies. J Natl Cancer Inst 2004;96:1015–22.doi:10.1093/jnci/djh185
      OpenUrlCrossRefPubMedWeb of Science
    44. 44.↵
      2. Huncharek M ,
      3. Muscat J ,
      4. Kupelnick B
      . Dairy products, dietary calcium and vitamin D intake as risk factors for prostate cancer: a meta-analysis of 26,769 cases from 45 observational studies. Nutr Cancer 2008;60:421–41.doi:10.1080/01635580801911779
      OpenUrlCrossRefPubMed
    45. 45.↵
      2. Qin LQ ,
      3. Hy X ,
      4. Wang PY , et al
      . Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies. Asia Pac J Clin Nutr 2007;16:467–76.
      OpenUrlPubMedWeb of Science
    46. 46.↵
      2. Gao X ,
      3. LaValley MP ,
      4. Tucker KL
      . Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. J Natl Cancer Inst 2005;97:1768–77.doi:10.1093/jnci/dji402
      OpenUrlCrossRefPubMedWeb of Science
    47. 47.↵
      2. Epstein MM ,
      3. Smith-Warner SA
      . Risk of prostate cancer with intake of dietary and total calcium: A pooled analysis of 14 prospective cohort studies. Cancer Prevention Research Conference: AACR International Conference on Frontiers in Cancer Prevention Research 2011:4.
    48. 48.↵
      2. Qin LQ ,
      3. Xu JY ,
      4. Wang PY , et al
      . Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies. Nutr Cancer 2004;48:22–7.doi:10.1207/s15327914nc4801_4
      OpenUrlCrossRefPubMedWeb of Science
    49. 49.↵
      2. Lane JA ,
      3. Oliver SE ,
      4. Appleby PN , et al
      . Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries. Eur J Clin Nutr 2017;71:274–83.doi:10.1038/ejcn.2016.162
      OpenUrl
    50. 50.↵
      2. Larsson SC ,
      3. Orsini N ,
      4. Wolk A
      . Milk, milk products and lactose intake and ovarian cancer risk: a meta-analysis of epidemiological studies. Int J Cancer 2006;118:431–41.doi:10.1002/ijc.21305
      OpenUrlCrossRefPubMedWeb of Science
    51. 51.↵
      2. Qin LQ ,
      3. Xu JY ,
      4. Wang PY , et al
      . Milk/dairy products consumption, galactose metabolism and ovarian cancer: meta-analysis of epidemiological studies. Eur J Cancer Prev 2005;14:13–19.doi:10.1097/00008469-200502000-00003
      OpenUrlCrossRefPubMedWeb of Science
    52. 52.↵
      2. Genkinger JM ,
      3. Hunter DJ ,
      4. Spiegelman D , et al
      . Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev 2006;15:364–72.doi:10.1158/1055-9965.EPI-05-0484
      OpenUrlAbstract/FREE Full Text
    53. 53.↵
      2. Liu J ,
      3. Tang W ,
      4. Sang L , et al
      . Milk, yogurt, and lactose intake and ovarian cancer risk: a meta-analysis. Nutr Cancer 2015;67:68–72.doi:10.1080/01635581.2014.956247
      OpenUrl
    54. 54.↵
      2. Filomeno M ,
      3. Bosetti C ,
      4. Bidoli E , et al
      . Mediterranean diet and risk of endometrial cancer: a pooled analysis of three Italian case-control studies. Br J Cancer 2015;112:1816–21.doi:10.1038/bjc.2015.153
      OpenUrl
    55. 55.↵
      2. Missmer SA ,
      3. Smith-Warner SA ,
      4. Spiegelman D , et al
      . Meat and dairy food consumption and breast cancer: a pooled analysis of cohort studies. Int J Epidemiol 2002;31:78–85.doi:10.1093/ije/31.1.78
      OpenUrlCrossRefPubMedWeb of Science
    56. 56.↵
      2. Boyd NF ,
      3. Martin LJ ,
      4. Noffel M , et al
      . A meta-analysis of studies of dietary fat and breast cancer risk. Br J Cancer 1993;68:627–36.doi:10.1038/bjc.1993.398
      OpenUrlPubMedWeb of Science
    57. 57.↵
      2. Li F ,
      3. An SL ,
      4. Zhou Y , et al
      . Milk and dairy consumption and risk of bladder cancer: a meta-analysis. Urology 2011;78:1298–305.doi:10.1016/j.urology.2011.09.002
      OpenUrlCrossRefPubMed
    58. 58.↵
      2. Mao QQ ,
      3. Dai Y ,
      4. Lin YW , et al
      . Milk consumption and bladder cancer risk: a meta-analysis of published epidemiological studies. Nutr Cancer 2011;63:1263–71.doi:10.1080/01635581.2011.614716
      OpenUrlCrossRefPubMed
    59. 59.↵
      2. Lee JE ,
      3. Hunter DJ ,
      4. Spiegelman D , et al
      . Intakes of coffee, tea, milk, soda and juice and renal cell cancer in a pooled analysis of 13 prospective studies. Int J Cancer 2007;121:2246–53.doi:10.1002/ijc.22909
      OpenUrlCrossRefPubMed
    60. 60.↵
      2. Yu Y ,
      3. Li H ,
      4. Xu K , et al
      . Dairy consumption and lung cancer risk: a meta-analysis of prospective cohort studies. Onco Targets Ther 2016;9:111–6.
      OpenUrl
    61. 61.↵
      2. Caini S ,
      3. Masala G ,
      4. Gnagnarella P , et al
      . Food of animal origin and risk of non-Hodgkin lymphoma and multiple myeloma: a review of the literature and meta-analysis. Crit Rev Oncol Hematol 2016;100:16–24.doi:10.1016/j.critrevonc.2016.02.011
      OpenUrl
    62. 62.↵
      2. Wang J ,
      3. Li X ,
      4. Zhang D
      . Dairy product consumption and risk of Non-Hodgkin Lymphoma: a meta-analysis. Nutrients 2016;8:120.doi:10.3390/nu8030120
      OpenUrl
    63. 63.↵
      2. Franceschi S ,
      3. Levi F ,
      4. Negri E , et al
      . Diet and thyroid cancer: a pooled analysis of four European case-control studies. Int J Cancer 1991;48:395–8.doi:10.1002/ijc.2910480315
      OpenUrlCrossRefPubMedWeb of Science
    64. 64.↵
      2. O’Sullivan TA ,
      3. Hafekost K ,
      4. Mitrou F , et al
      . Food sources of saturated fat and the association with mortality: a meta-analysis. Am J Public Health 2013;103:e31–42.doi:10.2105/AJPH.2013.301492
      OpenUrlCrossRefPubMed
    65. 65.↵
      2. Lu W ,
      3. Chen H ,
      4. Niu Y , et al
      . Dairy products intake and cancer mortality risk: a meta-analysis of 11 population-based cohort studies. Nutr J 2016;15:91.doi:10.1186/s12937-016-0210-9
      OpenUrl
    66. 66.↵
      2. Ganmaa D ,
      3. Wang PY ,
      4. Qin LQ , et al
      . Is milk responsible for male reproductive disorders? Med Hypotheses 2001;57:510–4.doi:10.1054/mehy.2001.1380
      OpenUrlCrossRefPubMedWeb of Science
    67. 67.↵
      2. Ganmaa D ,
      3. Sato A
      . The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers. Med Hypotheses 2005;65:1028–37.doi:10.1016/j.mehy.2005.06.026
      OpenUrlCrossRefPubMedWeb of Science
    68. 68.↵
      2. Calvo MS ,
      3. Whiting SJ ,
      4. Barton CN
      . Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr 2004;80:1710S–6.doi:10.1093/ajcn/80.6.1710S
      OpenUrlAbstract/FREE Full Text
    69. 69.↵
      World Cancer Research Fund/American Institute for Cancer Research. Diet, nutrition, physical activity and cancer: a global perspective. Continuous update project expert report. 2018. Available at dietandcancerreport.org (Accessed 09 Nov 2018).
    70. 70.↵
      World Cancer Research Fund/American Institute for Cancer Research. Continuous update project expert report 2018. Meat, fish and dairy products and the risk of cancer. Available at dietandcancerreport.org (Accessed 09 Nov 2018).

    Footnotes

    • Patient consent for publication Not required.

    • Contributors MMJ and RZ were involved in coordination of all aspects of this study, including protocol development and manuscript preparation. TG was involved in the development of search strategies for various databases. LG, LC, FF and JL were involved in the study selection process, data extraction and quality assessment. DD, PC and MP are experts in cancer research and provided content expertise during the design and conduct of the study. AMA-S, RZ and MMJ are experts in systematic review methodology and provided guidance on appropriate methodology for conducting this overview of reviews. All authors contributed to the design of the study and critically reviewed the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data can be obtained from the corresponding author on request.