Genetic predictors for fecal propionate and butyrate-producing microbiome pathway are not associated with colorectal cancer risk: A Mendelian randomization analysis Journal Article


Authors: Lu, Y.; Zhao, Y. C.; Chang-Claude, J.; Gruber, S. B.; Gsur, A.; Offit, K.; Vodickova, L.; Woods, M. O.; Nguyen, L. H.; Wade, K. H.; Carreras-Torres, R.; Moreno, V.; Buchanan, D. D.; Cotterchio, M.; Chan, A. T.; Phipps, A. I.; Peters, U.; Song, M.
Article Title: Genetic predictors for fecal propionate and butyrate-producing microbiome pathway are not associated with colorectal cancer risk: A Mendelian randomization analysis
Abstract: BACKGROUND: Mechanistic data indicate the benefit of short-chain fatty acids (SCFA) produced by gut microbial fermentation of fiber on colorectal cancer, but direct epidemiologic evidence is limited. A recent study identified SNPs for two SCFA traits (fecal propionate and butyrate-producing microbiome pathway PWY-5022) in Europeans and showed metabolic benefits. METHODS: We conducted a two-sample Mendelian randomization analysis of the genetic instruments for the two SCFA traits (three SNPs for fecal propionate and nine for PWY-5022) in relation to colorectal cancer risk in three large European genetic consortia of 58,131 colorectal cancer cases and 67,347 controls. We estimated the risk of overall colorectal cancer and conducted subgroup analyses by sex, age, and anatomic subsites of colorectal cancer. RESULTS: We did not observe strong evidence for an association of the genetic predictors for fecal propionate levels and the abundance of PWY-5022 with the risk of overall colorectal cancer, colorectal cancer by sex, or early-onset colorectal cancer (diagnosed at <50 years), with no evidence of heterogeneity or pleiotropy. When assessed by tumor subsites, we found weak evidence for an association between PWY-5022 and risk of rectal cancer (OR per 1-SD, 0.95; 95% confidence intervals, 0.91-0.99; P = 0.03) but it did not surpass multiple testing of subgroup analysis. CONCLUSIONS: Genetic instruments for fecal propionate levels and the abundance of PWY-5022 were not associated with colorectal cancer risk. IMPACT: Fecal propionate and PWY-5022 may not have a substantial influence on colorectal cancer risk. Future research is warranted to comprehensively investigate the effects of SCFA-producing bacteria and SCFAs on colorectal cancer risk. ©2022 American Association for Cancer Research.
Keywords: genetics; metabolism; colorectal neoplasms; chemistry; colorectal tumor; intestine flora; feces; microflora; microbiota; butyric acid derivative; butyrates; mendelian randomization analysis; propionic acid derivative; humans; human; gastrointestinal microbiome; fatty acids, volatile; propionates; volatile fatty acid
Journal Title: Cancer Epidemiology Biomarkers and Prevention
Volume: 32
Issue: 2
ISSN: 1055-9965
Publisher: American Association for Cancer Research  
Date Published: 2023-02-01
Start Page: 281
End Page: 286
Language: English
DOI: 10.1158/1055-9965.Epi-22-0861
PUBMED: 36512731
PROVIDER: scopus
PMCID: PMC9905300
DOI/URL:
Notes: Article -- Export Date: 1 March 2023 -- Source: Scopus
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  1. Kenneth Offit
    788 Offit