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Genetic Predictors for Fecal Propionate and Butyrate-Producing Microbiome Pathway Are Not Associated with Colorectal Cancer Risk: A Mendelian Randomization Analysis
Y. Lu, YC. Zhao, J. Chang-Claude, SB. Gruber, A. Gsur, K. Offit, L. Vodickova, MO. Woods, LH. Nguyen, KH. Wade, R. Carreras-Torres, V. Moreno, DD. Buchanan, M. Cotterchio, AT. Chan, AI. Phipps, U. Peters, M. Song
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 CA059045
NCI NIH HHS - United States
U01 CA182883
NCI NIH HHS - United States
U01 CA137088
NCI NIH HHS - United States
U01 CA164930
NCI NIH HHS - United States
R21 CA191312
NCI NIH HHS - United States
P30 CA008748
NCI NIH HHS - United States
R01 CA201407
NCI NIH HHS - United States
U01 AG018033
NIA NIH HHS - United States
P30 CA015704
NCI NIH HHS - United States
P30 CA006973
NCI NIH HHS - United States
U01 CA261961
NCI NIH HHS - United States
R01 CA263776
NCI NIH HHS - United States
NLK
Free Medical Journals
from 1991 to 1 year ago
Freely Accessible Science Journals
from 1991 to 12 months ago
Open Access Digital Library
from 1991-11-01
Open Access Digital Library
from 1991-11-01
- MeSH
- Butyrates * analysis metabolism MeSH
- Feces * chemistry microbiology MeSH
- Colorectal Neoplasms * epidemiology genetics metabolism MeSH
- Fatty Acids, Volatile analysis genetics metabolism MeSH
- Humans MeSH
- Mendelian Randomization Analysis MeSH
- Propionates * analysis metabolism MeSH
- Risk MeSH
- Gastrointestinal Microbiome * genetics physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Geographicals
- Europe MeSH
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.
Biomedical Centre Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Center for Cancer Research Medical University of Vienna Vienna Austria
Consortium for Biomedical Research in Epidemiology and Public Health Madrid Spain
Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada
Department of Biostatistics Harvard T H Chan School of Public Health Boston Massachusetts
Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain
Department of Epidemiology Harvard T H Chan School of Public Health Boston Massachusetts
Department of Epidemiology University of Washington School of Public Health Seattle Washington
Department of Medicine Memorial Sloan Kettering Cancer Center New York New York
Department of Medicine Weill Cornell Medical College New York New York
Department of Nutrition Harvard T H Chan School of Public Health Boston Massachusetts
Digestive Diseases and Microbiota Group Girona Biomedical Research Institute Salt Girona Spain
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Genetic Medicine and Family Clinic The Royal Melbourne Hospital Parkville Victoria Australia
Medical Research Council Integrative Epidemiology Unit University of Bristol Bristol United Kingdom
Public Health Sciences Division Fred Hutchinson Cancer Center Seattle Washington
University Cancer Center Hamburg Medical Center Hamburg Eppendorf Hamburg Germany
References provided by Crossref.org
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