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Cited by 86Nutritional Studies and DietCarcinogens and Genotoxicity AssessmentHead and Neck Cancer Studies

Association between dietary nitrate and nitrite intake and site-specific cancer risk: evidence from observational studies

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Xie, Li, Mo, Miao, Jia, Hui-Xun, Liang, Fei, Yuan, Jing, Zhu, Ji·2016·Oncotarget
DOI 10.18632/oncotarget.10917PMC PMC5302962
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Abstract

// Li Xie 1, 3, * , Miao Mo 1, 3, * , Hui-Xun Jia 1, 3 , Fei Liang 1, 3 , Jing Yuan 1, 3 , Ji Zhu 1, 2, 3 1 Clinical Statistics Center, Fudan University Shanghai Cancer Center, Shanghai, China 2 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, China 3 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Ji Zhu, email: leo.zhu@126.com Keywords: nitrate, nitrite, cancer, risk, meta-analysis Received: January 06, 2016 Accepted: July 18, 2016 Published: July 29, 2016 ABSTRACT Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30 th , 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted. Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity ( I 2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers.

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  • Nitrate from vegetables, which represent the main dietary source, has not been associated with an increased cancer risk and may even demonstrate protective properties in meta-analyses.

    “Nitrate from vegetables, which represent the main dietary source, has not been associated with an increased cancer risk and may even demonstrate protective properties in meta-analyses [278,279,280].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [278]

    The Discussion says vegetables are the major source of dietary nitrate, and the meta-analysis found an inverse association between dietary nitrate intake and gastric cancer risk. However, the paper says few included studies assessed nitrate by food source, so it does not establish a separate finding for nitrate from vegetables. Its protective finding is specific to gastric cancer, not cancer risk generally. The indexed copy provides section labels but no page numbers. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Methaemoglobinaemia is primarily clinically relevant in infants and in cases of contaminated water exposure.

    “it is primarily clinically relevant in infants and in cases of contaminated water exposure”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [278]

    The Introduction (page not provided) states that high nitrate exposure can cause methemoglobinemia in infants, supporting the infant-related part of the claim. It does not connect methemoglobinemia to contaminated water exposure or establish that these are the primary circumstances in which it is clinically relevant. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Nitrate and nitrite have historically been associated with potential toxic effects, including the risk of methaemoglobinaemia.

    “Beyond nitrosamine formation, nitrate and nitrite have also historically been associated with potential toxic effects, including the risk of methaemoglobinaemia [278,279,280].”

    From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [278]

    The Introduction states that high nitrate exposure can cause methemoglobinemia in infants and explains that ingested nitrate is converted to nitrite. It does not separately attribute methemoglobinemia risk to nitrite or establish the risk beyond infants. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Xie, L., Mo, M., Jia, H.-X., Liang, F., Yuan, J., & Zhu, J.
Affiliations
  • Shanghai Medical College of Fudan University (CN)
  • Clinical Statistics Center, Fudan University Shanghai Cancer Center, Shanghai, China
Corresponding author
  • Xie, Li
  • Mo, Miao
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2016-07-29
Volume
7
Issue
35
Pages
56915-56932
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.10917
PMC
PMC5302962
OpenAlex
W2503146442
Cited by
86
References
6
Citations by year
2026: 5 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 15 · 2021: 11 · 2020: 15 · 2019: 6 · 2018: 5 · 2017: 4
FWCI
4.96
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Keywords
dietary nitrate, dietary nitrite, cancer risk, gastric cancer, glioma, thyroid cancer, site-specific cancer
MeSH terms
Algorithms, Diet, Female, Humans, Male, Neoplasms, Nitrates, Nitrites, Risk, Observational Studies as Topic

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