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Association between folate intake and risk of head and neck squamous cell carcinoma : An overall and dose–response PRISMA meta-analysis

, MD, , MD, , MD, , MD, , MD, , MD


Wolters Kluwer Health

dose–response, folate, HNSCC, meta-analysis

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      The results of published studies about the relationships between folate intake and risk of head and neck squamous cell carcinoma (HNSCC) remained inconsistent. Hence, a comprehensive and dose–response meta-analysis was performed to clarify the association between folate intake and HNSCC risk.The electric searches of Pubmed, Medline, and EMBASE databases were performed to identify the studies examining the relationship between folate intake and HNSCC risk on April 5, 2017. According to the inclusion criteria, finally 9 studies were included in this meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. Dose–response analysis was conducted to quantitate the relationship between dietary folate intake and HNSCC risk.The pooled OR for assessing the risk of HNSCC and folate intake in the highest level versus lowest level was 0.505 (95% CI 0.387–0.623). The linearity model of dose–response analysis indicated that with increased 100 μg/d folate intake, the risk of HNSCC decreased 4.3% degree (OR 0.957, 95% CI 0.935–0.980).These results indicate that folate is a protective nutrient against HNSCC carcinogenesis.

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          Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.

            Author and article information

            Department of Oral and Maxillofacial Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
            Author notes
            []Correspondence: Zhigang Cheng, Department of Oral and Maxillofacial Surgery, The Central Hospital of Wuhan, Wuhan, China (e-mail: zhigangcheng888@ ).
            Medicine (Baltimore)
            Medicine (Baltimore)
            Wolters Kluwer Health
            October 2017
            20 October 2017
            : 96
            : 42
            Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

            This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Research Article
            Meta-Analysis of Observational Studies in Epidemiology
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            dose–response, folate, hnscc, meta-analysis


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