A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk-Reference-Cited by-同舟云学术

A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Published:2023-05-30 Issue:15 Volume:83 Page:2572-2583
ISSN:0008-5472
Container-title:Cancer Research
language:en
Short-container-title:

Author:

Aglago Elom K.¹^ORCID,Kim Andre²^ORCID,Lin Yi³^ORCID,Qu Conghui³^ORCID,Evangelou Marina¹^ORCID,Ren Yu¹^ORCID,Morrison John²^ORCID,Albanes Demetrius⁴^ORCID,Arndt Volker⁵^ORCID,Barry Elizabeth L.⁶^ORCID,Baurley James W.⁷⁸^ORCID,Berndt Sonja I.⁴^ORCID,Bien Stephanie A.³^ORCID,Bishop D. Timothy⁹^ORCID,Bouras Emmanouil¹⁰^ORCID,Brenner Hermann⁵¹¹¹²^ORCID,Buchanan Daniel D.¹³¹⁴¹⁵^ORCID,Budiarto Arif⁷¹⁶^ORCID,Carreras-Torres Robert¹⁷¹⁸^ORCID,Casey Graham¹⁹^ORCID,Cenggoro Tjeng Wawan⁷^ORCID,Chan Andrew T.²⁰²¹²²²³²⁴²⁵^ORCID,Chang-Claude Jenny²⁶²⁷^ORCID,Chen Xuechen⁵²⁸^ORCID,Conti David V.²^ORCID,Devall Matthew²⁹^ORCID,Diez-Obrero Virginia¹⁷³⁰³¹³²³³^ORCID,Dimou Niki³⁴^ORCID,Drew David²²^ORCID,Figueiredo Jane C.²³⁵^ORCID,Gallinger Steven³⁶^ORCID,Giles Graham G.³⁷³⁸³⁹^ORCID,Gruber Stephen B.⁴⁰^ORCID,Gsur Andrea⁴¹^ORCID,Gunter Marc J.³⁴^ORCID,Hampel Heather⁴⁰^ORCID,Harlid Sophia⁴²^ORCID,Hidaka Akihisa³^ORCID,Harrison Tabitha A.³^ORCID,Hoffmeister Michael⁵^ORCID,Huyghe Jeroen R.³^ORCID,Jenkins Mark A.³⁸^ORCID,Jordahl Kristina³^ORCID,Joshi Amit D.²²²⁴^ORCID,Kawaguchi Eric S.²^ORCID,Keku Temitope O.⁴³^ORCID,Kundaje Anshul⁴⁴⁴⁵^ORCID,Larsson Susanna C.⁴⁶^ORCID,Marchand Loic Le⁴⁷^ORCID,Lewinger Juan Pablo²^ORCID,Li Li²⁹^ORCID,Lynch Brigid M.³⁷⁴⁸⁴⁹^ORCID,Mahesworo Bharuno⁷^ORCID,Mandic Marko⁵²⁸^ORCID,Obón-Santacana Mireia¹⁷³⁰³¹^ORCID,Moreno Victor¹⁷³⁰³¹⁵⁰^ORCID,Murphy Neil³⁴^ORCID,Nan Hongmei⁵¹⁵²^ORCID,Nassir Rami⁵³^ORCID,Newcomb Polly A.³⁵⁴^ORCID,Ogino Shuji²³²⁴⁵⁵⁵⁶^ORCID,Ose Jennifer⁵⁷⁵⁸^ORCID,Pai Rish K.⁵⁹^ORCID,Palmer Julie R.⁶⁰^ORCID,Papadimitriou Nikos³⁴^ORCID,Pardamean Bens⁷^ORCID,Peoples Anita R.⁵⁷⁵⁸^ORCID,Platz Elizabeth A.⁶¹^ORCID,Potter John D.³⁵⁴⁶²^ORCID,Prentice Ross L.³^ORCID,Rennert Gad⁶³⁶⁴⁶⁵^ORCID,Ruiz-Narvaez Edward⁶⁶^ORCID,Sakoda Lori C.³⁶⁷^ORCID,Scacheri Peter C.⁶⁸^ORCID,Schmit Stephanie L.⁶⁹^ORCID,Schoen Robert E.⁷⁰^ORCID,Shcherbina Anna⁴⁴⁴⁵^ORCID,Slattery Martha L.⁷¹^ORCID,Stern Mariana C.²^ORCID,Su Yu-Ru³^ORCID,Tangen Catherine M.⁷²^ORCID,Thibodeau Stephen N.⁷³^ORCID,Thomas Duncan C.²^ORCID,Tian Yu²⁶⁷⁴^ORCID,Ulrich Cornelia M.⁵⁷⁵⁸^ORCID,van Duijnhoven Franzel JB⁷⁵^ORCID,Van Guelpen Bethany⁴²⁷⁶^ORCID,Visvanathan Kala⁶¹^ORCID,Vodicka Pavel⁷⁷⁷⁸⁷⁹^ORCID,Wang Jun²^ORCID,White Emily³⁵⁴^ORCID,Wolk Alicja⁴⁶^ORCID,Woods Michael O.⁸⁰^ORCID,Wu Anna H.²^ORCID,Zemlianskaia Natalia²^ORCID,Hsu Li³⁸¹^ORCID,Gauderman W. James²^ORCID,Peters Ulrike³⁵⁴^ORCID,Tsilidis Konstantinos K.¹¹⁰^ORCID,Campbell Peter T.⁸²^ORCID

Affiliation:

1. 1Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.

2. 2Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.

3. 3Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

4. 4Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

5. 5Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

6. 6Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.

7. 7Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.

8. 8BioRealm LLC, Walnut, California.

9. 9Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.

10. 10Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

11. 11Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

12. 12German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

13. 13Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.

14. 14University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.

15. 15Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.

16. 16Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.

17. 17ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

18. 18Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.

19. 19Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.

20. 20Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

21. 21Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

22. 22Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

23. 23Broad Institute of Harvard and MIT, Cambridge, Massachusetts.

24. 24Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

25. 25Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

26. 26Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

27. 27University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.

28. 28Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.

29. 29Department of Family Medicine, University of Virginia, Charlottesville, Virginia.

30. 30Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain.

31. 31Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.

32. 32Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.

33. 33Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

34. 34Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.

35. 35Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

36. 36Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

37. 37Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

38. 38Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.

39. 39Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.

40. 40Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte California.

41. 41Center for Cancer Research, Medical University of Vienna, Vienna, Austria.

42. 42Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.

43. 43Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina.

44. 44Department of Genetics, Stanford University, Stanford, California.

45. 45Department of Computer Science, Stanford University, Stanford, California.

46. 46Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

47. 47University of Hawaii Cancer Center, Honolulu, Hawaii.

48. 48Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.

49. 49Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.

50. 50Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.

51. 51Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indianapolis, Indiana.

52. 52IU Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana.

53. 53Department of Pathology, School of Medicine, Umm Al-Qura'a University, Mecca, Saudi Arabia.

54. 54Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.

55. 55Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

56. 56Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts.

57. 57Huntsman Cancer Institute, Salt Lake City, Utah.

58. 58Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.

59. 59Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, Arizona.

60. 60Department of Medicine, Boston University School of Medicine, Slone Epidemiology Center, Boston University, Boston, Massachusetts.

61. 61Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

62. 62Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.

63. 63Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.

64. 64Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

65. 65Clalit National Cancer Control Center, Haifa, Israel.

66. 66Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan.

67. 67Division of Research, Kaiser Permanente Northern California, Oakland, California.

68. 68Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio.

69. 69Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio.

70. 70Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

71. 71Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

72. 72SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.

73. 73Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

74. 74School of Public Health, Capital Medical University, Beijing, China.

75. 75Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.

76. 76Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.

77. 77Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

78. 78Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.

79. 79Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.

80. 80Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.

81. 81Department of Biostatistics, University of Washington, Seattle, Washington.

82. 82Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.

Abstract

Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

Funder

National Institutes of Health

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/cancerres/article-pdf/doi/10.1158/0008-5472.CAN-22-3713/3336399/can-22-3713.pdf

Reference55 articles.

1. An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites;Papadimitriou;Nat Commun,2021

2. Lifestyle and dietary environmental factors in colorectal cancer susceptibility;Murphy;Mol Aspects Med,2019

3. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States;Islami;CA Cancer J Clin,2018

4. Population attributable risk for colorectal and breast cancer in England, Wales, Scotland, Northern Ireland, and the United Kingdom [version 1; peer review: 1 approved, 1 not approved];Goon;AMRC Open Research,2021

5. Obesity: a certain and avoidable cause of cancer;Campbell;Lancet,2014

Cited by 3 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes;Current Issues in Molecular Biology;2024-06-26

2. Unveiling challenges in Mendelian randomization for gene–environment interaction;Genetic Epidemiology;2024-02-29

3. A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator;2024-02-13