Abstract
BackgroundColorectal cancer (CRC) is a major cause of cancer deaths worldwide. Accumulating evidence suggests a potentially important role of colorectal infection with Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis. We conducted a systematic review, including both a qualitative synthesis and a meta-analysis, to synthesize the evidence from the epidemiological literature on the association between F. nucleatum detection in the colon/rectum and CRC.MethodsA systematic literature search of Ovid MEDLINE(R), Embase, Web of Science Core Collection, EBM Reviews—Cochrane Database of Systematic Reviews, and CINAHL Plus with Full Text was conducted using earliest inclusive dates up to 4 October 2020. Eligible studies were original, comparative observational studies that reported results on colorectal F. nucleatum detection and CRC. Two independent reviewers extracted the relevant information. Odds ratio (OR) estimates were pooled across studies using the random effects model. Newcastle-Ottawa scale was used to critically appraise study quality.ResultsTwenty-four studies were included in the systematic review, of which 12 were included in the meta-analysis. Studies investigated F. nucleatum in feces, colorectal tissue samples, or both. In most studies included in the systematic review, the load of F. nucleatum was higher, on average, in specimens from CRC patients than in those from CRC-free controls. Meta-analysis showed a positive association between F. nucleatum detection in colorectal specimens and CRC (OR = 8.3; 95% confidence interval (95% CI) 5.2 to 13.0).ConclusionsThe results of this systematic review suggest that F. nucleatum in the colon/rectum is associated with CRC.Systematic review registrationThis systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 10, 2018 (registration number CRD42018095866).
Highlights
Colorectal cancer (CRC) is a major cause of cancer deaths worldwide
Systematic review registration: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on July 10, 2018
This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018
Summary
Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Accumulating evidence suggests a potentially important role of colorectal infection with Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis. In 2011, Sears and Pardoll suggested that bacteria are the main drivers of the intestinal mucosa immune response and subsequent changes in the function and genetics of epithelial cells, which support oncogenic transformation [14] These ideas have rapidly gained credibility due to important discoveries on the role of gut microbial dysbiosis and of the bacterium Fusobacterium nucleatum (F. nucleatum) in colorectal carcinogenesis [15,16,17,18,19,20,21,22,23,24,25]. The protein Fap inhibits the activity of immune cells and potentiates the progression of CCR [32, 33] This suggests that F. nucleatum may participate in the colorectal tumor process and be a prooncogenic bacterium. Mouse tumors (APC +/−) exposed to F. nucleatum have a proinflammatory expression, similar to that observed in human colorectal tumors positive for F. nucleatum [18]
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