• This record comes from PubMed

Genetic Predictors for Fecal Propionate and Butyrate-Producing Microbiome Pathway Are Not Associated with Colorectal Cancer Risk: A Mendelian Randomization Analysis

. 2023 Feb 06 ; 32 (2) : 281-286.

Language English Country United States Media print

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/pmid36512731

Grant support
R01 CA067941 NCI NIH HHS - United States
U01 HG004438 NHGRI NIH HHS - United States
U01 HG004446 NHGRI NIH HHS - United States
K05 CA154337 NCI NIH HHS - United States
U01 CA164930 NCI NIH HHS - United States
P30 CA076292 NCI NIH HHS - United States
HHSN268201100003I NHLBI NIH HHS - United States
P01 CA196569 NCI NIH HHS - United States
U01 CA067941 NCI NIH HHS - United States
R01 CA059045 NCI NIH HHS - United States
HHSN268201100001I NHLBI NIH HHS - United States
R01 CA197350 NCI NIH HHS - United States
R01 CA076366 NCI NIH HHS - United States
R35 CA197735 NCI NIH HHS - United States
U10 CA037429 NCI NIH HHS - United States
U01 CA182883 NCI NIH HHS - United States
R01 CA072520 NCI NIH HHS - United States
P01 CA087969 NCI NIH HHS - United States
P30 CA015704 NCI NIH HHS - United States
P30 DK043351 NIDDK NIH HHS - United States
HHSN268201100004I NHLBI NIH HHS - United States
P30 CA006973 NCI NIH HHS - United States
Z01 CP010200 Intramural NIH HHS - United States
P01 CA055075 NCI NIH HHS - United States
S10 OD028685 NIH HHS - United States
R01 CA151993 NCI NIH HHS - United States
HHSN268201100046C NHLBI NIH HHS - United States
P30 DK034987 NIDDK NIH HHS - United States
R01 CA048998 NCI NIH HHS - United States
U01 CA137088 NCI NIH HHS - United States
R01 CA189184 NCI NIH HHS - United States
U01 CA167552 NCI NIH HHS - United States
HHSN268201100003C WHI NIH HHS - United States
U01 CA261961 NCI NIH HHS - United States
U24 CA074794 NCI NIH HHS - United States
R01 CA263776 NCI NIH HHS - United States
R01 CA066635 NCI NIH HHS - United States
R21 CA191312 NCI NIH HHS - United States
U01 CA206110 NCI NIH HHS - United States
R01 CA137178 NCI NIH HHS - United States
U01 CA074794 NCI NIH HHS - United States
HHSN268201200008C NHLBI NIH HHS - United States
R01 CA242218 NCI NIH HHS - United States
P30 CA008748 NCI NIH HHS - United States
U01 CA167551 NCI NIH HHS - United States
P30 CA014089 NCI NIH HHS - United States
R01 CA081488 NCI NIH HHS - United States
HHSN271201100004C NIA NIH HHS - United States
R01 CA201407 NCI NIH HHS - United States
R01 CA063464 NCI NIH HHS - United States
P01 CA033619 NCI NIH HHS - United States
U01 CA086308 NCI NIH HHS - United States
UM1 CA186107 NCI NIH HHS - United States
HHSN268201100002C WHI NIH HHS - United States
R01 CA207371 NCI NIH HHS - United States
R03 CA153323 NCI NIH HHS - United States
R01 CA042182 NCI NIH HHS - United States
R01 CA054281 NCI NIH HHS - United States
T32 ES013678 NIEHS NIH HHS - United States
R01 CA136726 NCI NIH HHS - United States
P30 CA016058 NCI NIH HHS - United States
UM1 CA167552 NCI NIH HHS - United States
K05 CA152715 NCI NIH HHS - United States
U01 CA122839 NCI NIH HHS - United States
HHSN268201100002I NHLBI NIH HHS - United States
U01 CA074783 NCI NIH HHS - United States
U01 CA084968 NCI NIH HHS - United States
KL2 TR000421 NCATS NIH HHS - United States
UM1 CA182883 NCI NIH HHS - United States
HHSN268201200008I NHLBI NIH HHS - United States
R37 CA054281 NCI NIH HHS - United States
HHSN268201100001C WHI NIH HHS - United States
HHSN268201100004C WHI NIH HHS - United States
R01 CA097325 NCI NIH HHS - United States
HHSN268201700006C NHLBI NIH HHS - United States
U19 CA148107 NCI NIH HHS - United States
U01 AG018033 NIA NIH HHS - United States

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

Clinical and Translational Epidemiology Unit Massachusetts General Hospital Harvard Medical School Boston Massachusetts

Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute L'Hospitalet de Llobregat Barcelona Spain

Colorectal Oncogenomic Group Department of Clinical Pathology University of Melbourne Parkville Victoria Australia

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 Immunology and Infectious Diseases Harvard T H Chan School of Public Health Boston Massachusetts

Department of Medical Oncology and Therapeutics Research City of Hope National Medical Center Duarte California

Department of Medicine Channing Division of Network Medicine Brigham and Women's Hospital Harvard Medical School Boston Massachusetts

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 Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

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 Biomedical Sciences Memorial University of Newfoundland St John's Newfoundland and Labrador Canada

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Gastroenterology Clinical and Translational Epidemiology Unit Massachusetts General Hospital Harvard Medical School Boston Massachusetts

Genetic Medicine and Family Clinic The Royal Melbourne Hospital Parkville Victoria Australia

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Medical Research Council Integrative Epidemiology Unit University of Bristol Bristol United Kingdom

Oncology Data Analytics Program Catalan Institute of Oncology L'Hospitalet de Llobregat Barcelona Spain

Prevention and Cancer Control Clinical Institutes and Quality Programs Ontario Health Toronto Ontario Canada

Public Health Sciences Division Fred Hutchinson Cancer Center Seattle Washington

University Cancer Center Hamburg Medical Center Hamburg Eppendorf Hamburg Germany

Victorian Comprehensive Cancer Centre University of Melbourne Centre for Cancer Research Parkville Victoria Australia

See more in PubMed

Song M, Chan AT, Sun J. Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer. Gastroenterology 2020;158:322–340. PubMed PMC

Thomas AM, Manghi P, Asnicar F, Pasolli E, Armanini F, Zolfo M, et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nature Medicine 2019;25:667–678. PubMed PMC

Chen HM, Yu YN, Wang JL, Lin YW, Kong X, Yang CQ, et al. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. American Journal of Clinical Nutrition 2013;97:1044–1052. PubMed

Sanna S, van Zuydam NR, Mahajan A, Kurilshikov A, Vich Vila A, Võsa U, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nature Genetics 2019;51:600–605. PubMed PMC

Murphy N, Song M, Papadimitriou N, Carreras-Torres R, Langenberg C, Martin RM, et al. Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis. JNCI: Journal of the National Cancer Institute 2022;114:740–752. PubMed PMC

Huyghe JR, Bien SA, Harrison TA, Kang HM, Chen S, Schmit SL, et al. Discovery of common and rare genetic risk variants for colorectal cancer. Nature Genetics 2019;51:76–87. PubMed PMC

Wang M, Spiegelman D, Kuchiba A, Lochhead P, Kim S, Chan AT, et al. Statistical methods for studying disease subtype heterogeneity. Statistics in Medicine 2016;35:782–800. PubMed PMC

Sze MA, Topçuoğlu BD, Lesniak NA, Ruffin MT, Schloss PD, Fraser CM. Fecal Short-Chain Fatty Acids Are Not Predictive of Colonic Tumor Status and Cannot Be Predicted Based on Bacterial Community Structure. mBio 2019;10:e01454–01419. PubMed PMC

Find record

Citation metrics

Archiving options