Genetic Predictors for Fecal Propionate and Butyrate-Producing Microbiome Pathway Are Not Associated with Colorectal Cancer Risk: A Mendelian Randomization Analysis-Reference-Cited by-同舟云学术

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

Published:2022-12-13 Issue:2 Volume:32 Page:281-286
ISSN:1055-9965
Container-title:Cancer Epidemiology, Biomarkers & Prevention
language:en
Short-container-title:

Author:

Lu Yujia¹^ORCID,Zhao Yu Chen¹^ORCID,Chang-Claude Jenny²³^ORCID,Gruber Stephen B.⁴^ORCID,Gsur Andrea⁵^ORCID,Offit Kenneth⁶⁷⁸^ORCID,Vodickova Ludmila⁹¹⁰¹¹^ORCID,Woods Michael O.¹²^ORCID,Nguyen Long H.¹³¹⁴^ORCID,Wade Kaitlin H.¹⁵^ORCID,Carreras-Torres Robert¹⁶¹⁷^ORCID,Moreno Victor¹⁶¹⁸¹⁹²⁰^ORCID,Buchanan Daniel D.²¹²²²³^ORCID,Cotterchio Michelle²⁴²⁵^ORCID,Chan Andrew T.¹³²⁶²⁷^ORCID,Phipps Amanda I.²⁸²⁹^ORCID,Peters Ulrike²⁸²⁹^ORCID,Song Mingyang¹¹³³⁰^ORCID

Affiliation:

1. 1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

2. 2Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

3. 3University Cancer Center Hamburg (UCCH), Medical Center Hamburg-Eppendorf, Hamburg, Germany.

4. 4Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, California.

5. 5Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

6. 6Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

7. 7Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.

8. 8Department of Medicine, Weill Cornell Medical College, New York, New York.

9. 9Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

10. 10Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.

11. 11Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.

12. 12Division of Biomedical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.

13. 13Division of Gastroenterology, Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

14. 14Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

15. 15Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.

16. 16Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

17. 17Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.

18. 18Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.

19. 19Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.

20. 20Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.

21. 21Colorectal Oncogenomic Group, Department of Clinical Pathology, University of Melbourne, Parkville, Victoria, Australia.

22. 22Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Parkville, Victoria, Australia.

23. 23Genetic Medicine and Family Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.

24. 24Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Toronto, Ontario, Canada.

25. 25Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

26. 26Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

27. 27Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

28. 28Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.

29. 29Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington.

30. 30Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Abstract

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.

Funder

National Institutes of Health

National Cancer Institute

Office of Research Infrastructure Programs, National Institutes of Health

National Institute on Aging

American Institute for Cancer Research

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

Link

https://aacrjournals.org/cebp/article-pdf/doi/10.1158/1055-9965.EPI-22-0861/3231291/epi-22-0861.pdf