Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer-Reference-Cited by-同舟云学术

Tissue-specific genetic variation suggests distinct molecular pathways between body shape phenotypes and colorectal cancer

Published:2024-04-19 Issue:16 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Peruchet-Noray Laia¹²^ORCID,Sedlmeier Anja M.³⁴⁵^ORCID,Dimou Niki¹^ORCID,Baurecht Hansjörg⁵^ORCID,Fervers Béatrice⁶^ORCID,Fontvieille Emma¹,Konzok Julian⁵^ORCID,Tsilidis Kostas K.⁷⁸^ORCID,Christakoudi Sofia⁷⁹,Jansana Anna¹^ORCID,Cordova Reynalda¹¹⁰^ORCID,Bohmann Patricia⁵^ORCID,Stein Michael J.⁵^ORCID,Weber Andrea⁵^ORCID,Bézieau Stéphane¹¹^ORCID,Brenner Hermann¹²¹³¹⁴,Chan Andrew T.¹⁵^ORCID,Cheng Iona¹⁶,Figueiredo Jane C.¹⁷,Garcia-Etxebarria Koldo¹⁸¹⁹^ORCID,Moreno Victor²²⁰²¹²²^ORCID,Newton Christina C.²³^ORCID,Schmit Stephanie L.²⁴²⁵^ORCID,Song Mingyang¹⁵²⁶^ORCID,Ulrich Cornelia M.²⁷^ORCID,Ferrari Pietro¹^ORCID,Viallon Vivian¹^ORCID,Carreras-Torres Robert²⁸^ORCID,Gunter Marc J.¹⁷^ORCID,Freisling Heinz¹^ORCID

Affiliation:

1. International Agency for Research on Cancer (IARC/WHO), Nutrition and Metabolism Branch, 69366 Lyon CEDEX 07, France.

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

3. Center for Translational Oncology, University Hospital Regensburg, Regensburg, Germany.

4. Bavarian Cancer Research Center (BZKF), Regensburg, Germany.

5. Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.

6. Département Prévention Cancer Environnement, Centre Léon Bérard, Lyon, France.

7. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK.

8. Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

9. Department of Inflammation Biology, School of Immunology & Microbial Sciences, King’s College London, London, UK.

10. Department of Nutritional Sciences, University of Vienna, Vienna, Austria.

11. Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.

12. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

13. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

14. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

15. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

16. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.

17. Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

18. Biodonostia, Gastrointestinal Genetics Group, San Sebastián, Spain.

19. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

20. Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet del Llobregat, 08908 Barcelona, Spain.

21. ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain.

22. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain.

23. Department of Population Science, American Cancer Society, Atlanta, GA, USA.

24. Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

25. Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH, USA.

26. Departments of Epidemiology and Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

27. Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.

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

Abstract

It remains unknown whether adiposity subtypes are differentially associated with colorectal cancer (CRC). To move beyond single-trait anthropometric indicators, we derived four multi-trait body shape phenotypes reflecting adiposity subtypes from principal components analysis on body mass index, height, weight, waist-to-hip ratio, and waist and hip circumference. A generally obese (PC1) and a tall, centrally obese (PC3) body shape were both positively associated with CRC risk in observational analyses in 329,828 UK Biobank participants (3728 cases). In genome-wide association studies in 460,198 UK Biobank participants, we identified 3414 genetic variants across four body shapes and Mendelian randomization analyses confirmed positive associations of PC1 and PC3 with CRC risk (52,775 cases/45,940 controls from GECCO/CORECT/CCFR). Brain tissue–specific genetic instruments, mapped to PC1 through enrichment analysis, were responsible for the relationship between PC1 and CRC, while the relationship between PC3 and CRC was predominantly driven by adipose tissue–specific genetic instruments. This study suggests distinct putative causal pathways between adiposity subtypes and CRC.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adj1987

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