Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region-Reference-Cited by-同舟云学术

Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Published:2022-02-24 Issue:5 Volume:31 Page:1077-1089
ISSN:1055-9965
Container-title:Cancer Epidemiology, Biomarkers & Prevention
language:en
Short-container-title:

Author:

Jordahl Kristina M.¹²^ORCID,Shcherbina Anna³⁴^ORCID,Kim Andre E.⁵,Su Yu-Ru²,Lin Yi²,Wang Jun⁵,Qu Conghui²,Albanes Demetrius⁶,Arndt Volker⁷^ORCID,Baurley James W.⁸⁹,Berndt Sonja I.⁶,Bien Stephanie A.²^ORCID,Bishop D. Timothy¹⁰^ORCID,Bouras Emmanouil¹¹,Brenner Hermann⁷¹²¹³^ORCID,Buchanan Daniel D.¹⁴¹⁵¹⁶^ORCID,Budiarto Arif⁸¹⁷,Campbell Peter T.¹⁸^ORCID,Carreras-Torres Robert¹⁹^ORCID,Casey Graham²⁰,Cenggoro Tjeng Wawan⁸,Chan Andrew T.²¹²²²³²⁴²⁵²⁶^ORCID,Conti David V.²⁷,Dampier Christopher H.²⁰^ORCID,Devall Matthew A.²⁰,Díez-Obrero Virginia¹⁹²⁸²⁹³⁰,Dimou Niki³¹^ORCID,Drew David A.³²^ORCID,Figueiredo Jane C.³³³⁴^ORCID,Gallinger Steven³⁵,Giles Graham G.³⁶³⁷³⁸^ORCID,Gruber Stephen B.²⁷^ORCID,Gsur Andrea³⁹^ORCID,Gunter Marc J.⁴⁰^ORCID,Hampel Heather⁴¹^ORCID,Harlid Sophia⁴²^ORCID,Harrison Tabitha A.²^ORCID,Hidaka Akihisa²^ORCID,Hoffmeister Michael⁷^ORCID,Huyghe Jeroen R.²^ORCID,Jenkins Mark A.³⁷,Joshi Amit D.²³²⁵,Keku Temitope O.⁴³,Larsson Susanna C.⁴⁴^ORCID,Le Marchand Loic⁴⁵,Lewinger Juan Pablo³⁴,Li Li⁴⁶,Mahesworo Bharuno⁸^ORCID,Moreno Victor²⁸³⁰⁴⁷⁴⁸^ORCID,Morrison John L.³⁴^ORCID,Murphy Neil⁴⁰,Nan Hongmei⁴⁹⁵⁰,Nassir Rami⁵¹^ORCID,Newcomb Polly A.¹²,Obón-Santacana Mireia⁵²,Ogino Shuji²⁵⁵³⁵⁴⁵⁵^ORCID,Ose Jennifer⁵⁶⁵⁷^ORCID,Pai Rish K.⁵⁸^ORCID,Palmer Julie R.⁵⁹^ORCID,Papadimitriou Nikos³¹,Pardamean Bens⁸,Peoples Anita R.⁵⁷⁶⁰^ORCID,Pharoah Paul D.P.⁶¹^ORCID,Platz Elizabeth A.⁶²^ORCID,Potter John D.²^ORCID,Prentice Ross L.²,Rennert Gad⁶³⁶⁴⁶⁵^ORCID,Ruiz-Narvaez Edward⁶⁶^ORCID,Sakoda Lori C.²⁶⁷^ORCID,Scacheri Peter C.⁶⁸,Schmit Stephanie L.⁶⁹⁷⁰^ORCID,Schoen Robert E.⁷¹^ORCID,Slattery Martha L.⁷²^ORCID,Stern Mariana C.²⁷^ORCID,Tangen Catherine M.⁷³,Thibodeau Stephen N.⁷⁴,Thomas Duncan C.²⁷^ORCID,Tian Yu⁷⁵⁷⁶^ORCID,Tsilidis Konstantinos K.¹¹⁷⁷^ORCID,Ulrich Cornelia M.⁵⁷⁶⁰^ORCID,van Duijnhoven Franzel J.B.⁷⁸^ORCID,Van Guelpen Bethany⁴²⁷⁹^ORCID,Visvanathan Kala⁶²^ORCID,Vodicka Pavel⁸⁰⁸¹⁸²,White Emily¹²,Wolk Alicja⁴⁴^ORCID,Woods Michael O.⁸³^ORCID,Wu Anna H.³⁴,Zemlianskaia Natalia²⁷,Chang-Claude Jenny⁷⁵⁸⁴^ORCID,Gauderman W. James²⁷^ORCID,Hsu Li²⁸⁵^ORCID,Kundaje Anshul³⁴^ORCID,Peters Ulrike¹²^ORCID

Affiliation:

1. 1Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.

2. 2Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

3. 3Department of Genetics, Stanford University, Stanford, California.

4. 4Department of Computer Science, Stanford University, Stanford, California.

5. 5Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

6. 6Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

7. 7Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

8. 8Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.

9. 9BioRealm LLC, Walnut, California.

10. 10Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.

11. 11Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

12. 12Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

13. 13German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

14. 14Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.

15. 15University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.

16. 16Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.

17. 17Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.

18. 18Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.

19. 19Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

20. 20Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.

21. 21Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

22. 22Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

23. 23Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

24. 24Broad Institute of Harvard and MIT, Cambridge, Massachusetts.

25. 25Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

26. 26Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

27. 27Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.

28. 28Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

29. 29Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.

30. 30Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.

31. 31Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.

32. 32Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

33. 33Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

34. 34Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

35. 35Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

36. 36Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

37. 37Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.

38. 38Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.

39. 39Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.

40. 40Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.

41. 41Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

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. 44Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

45. 45University of Hawaii Cancer Center, Honolulu, Hawaii.

46. 46Department of Family Medicine, University of Virginia, Charlottesville, Virginia.

47. 47CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

48. 48ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

49. 49Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indianapolis, Indiana.

50. 50IU Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana.

51. 51Department of Pathology, School of Medicine, Umm Al-Qura'a University, Saudi Arabia.

52. 52Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Avda Gran Via Barcelona 199–203, 08908L'Hospitalet de Llobregat, Barcelona, Spain.

53. 53Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

54. 54Harvard Medical School, Boston, Massachusetts.

55. 55Broad Institute of MIT and Harvard, Cambridge, Massachusetts.

56. 56Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

57. 57Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.

58. 58Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, Arizona.

59. 59Slone Epidemiology Center at Boston University, Boston, Massachusetts.

60. 60Huntsman Cancer Institute, Salt Lake City, Utah.

61. 61Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

62. 62Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

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. 70Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, Ohio.

71. 71Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

72. 72Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

73. 73SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.

74. 74Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

75. 75Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

76. 76School of Public Health, Capital Medical University, Beijing, China.

77. 77Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.

78. 78Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.

79. 79Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.

80. 80Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

81. 81Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.

82. 82Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.

83. 83Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.

84. 84University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.

85. 85Department of Biostatistics, University of Washington, Seattle, Washington.

Abstract

Abstract Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1–28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose–response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06–1.17; OR for AA genotype = 1.22; 95% CI, 1.14–1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

Funder

National Cancer Institute National Institutes of Health U.S. Department of Health and Human Services

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

Link

https://aacrjournals.org/cebp/article-pdf/doi/10.1158/1055-9965.EPI-21-1003/3115147/epi-21-1003.pdf

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