Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort-Reference-Cited by-同舟云学术

Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort

Published:2023-01-09 Issue:3 Volume:32 Page:353-362
ISSN:1055-9965
Container-title:Cancer Epidemiology, Biomarkers & Prevention
language:en
Short-container-title:

Author:

Su Yu-Ru¹²^ORCID,Sakoda Lori C.²³⁴^ORCID,Jeon Jihyoun⁵^ORCID,Thomas Minta²^ORCID,Lin Yi²^ORCID,Schneider Jennifer L.³^ORCID,Udaltsova Natalia³^ORCID,Lee Jeffrey K.³⁶^ORCID,Lansdorp-Vogelaar Iris⁷^ORCID,Peterse Elisabeth F.P.⁷^ORCID,Zauber Ann G.⁸^ORCID,Zheng Jiayin²^ORCID,Zheng Yingye²^ORCID,Hauser Elizabeth⁹^ORCID,Baron John A.¹⁰^ORCID,Barry Elizabeth L.¹¹^ORCID,Bishop D. Timothy¹²^ORCID,Brenner Hermann¹³^ORCID,Buchanan Daniel D.¹⁴^ORCID,Burnett-Hartman Andrea¹⁵^ORCID,Campbell Peter T.¹⁶^ORCID,Casey Graham¹⁷^ORCID,Castellví-Bel Sergi¹⁸^ORCID,Chan Andrew T.¹⁹^ORCID,Chang-Claude Jenny²⁰^ORCID,Figueiredo Jane C.²¹^ORCID,Gallinger Steven J.²²^ORCID,Giles Graham G.²³^ORCID,Gruber Stephen B.²⁴²⁵^ORCID,Gsur Andrea²⁶^ORCID,Gunter Marc J.²⁷^ORCID,Hampe Jochen²⁸^ORCID,Hampel Heather²⁹^ORCID,Harrison Tabitha A.²^ORCID,Hoffmeister Michael¹³^ORCID,Hua Xinwei²^ORCID,Huyghe Jeroen R.²^ORCID,Jenkins Mark A.³⁰^ORCID,Keku Temitope O.³¹^ORCID,Marchand Loic Le³²^ORCID,Li Li³³^ORCID,Lindblom Annika³⁴^ORCID,Moreno Victor³⁵^ORCID,Newcomb Polly A.²^ORCID,Pharoah Paul D.P.³⁶^ORCID,Platz Elizabeth A.³⁷^ORCID,Potter John D.²^ORCID,Qu Conghui²^ORCID,Rennert Gad³⁸^ORCID,Schoen Robert E.³⁹^ORCID,Slattery Martha L.⁴⁰^ORCID,Song Mingyang⁴¹^ORCID,van Duijnhoven Fränzel J.B.⁴²^ORCID,Van Guelpen Bethany⁴³⁴⁴^ORCID,Vodicka Pavel⁴⁵⁴⁶^ORCID,Wolk Alicja⁴⁷^ORCID,Woods Michael O.⁴⁸^ORCID,Wu Anna H.²⁴^ORCID,Hayes Richard B.⁴⁹^ORCID,Peters Ulrike²^ORCID,Corley Douglas A.³^ORCID,Hsu Li²^ORCID

Affiliation:

1. 1Biostatistics Unit, Kaiser Permanente Washington Health Research Institute, Seattle, Washington.

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

3. 3Division of Research, Kaiser Permanente Northern California, Oakland, California.

4. 4Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California.

5. 5Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.

6. 6Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, California.

7. 7Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

8. 8Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

9. 9VA Cooperative Studies Program Epidemiology Center, Durham Veterans Affairs Health Care System, Durham, North Carolina.

10. 10Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

11. 11Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.

12. 12Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.

13. 13Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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

15. 15Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado.

16. 16Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.

17. 17Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.

18. 18Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.

19. 19Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

20. 20Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

21. 21Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

22. 22Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

23. 23Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

24. 24Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

25. 25USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.

26. 26Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.

27. 27Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.

28. 28Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.

29. 29Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

30. 30Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.

31. 31Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina.

32. 32University of Hawaii Cancer Center, Honolulu, Hawaii.

33. 33Department of Family Medicine, University of Virginia, Charlottesville, Virginia.

34. 34Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

35. 35Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

36. 36Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

37. 37Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

38. 38Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center and Technion-Israel Institute of Technology, Haifa, Israel.

39. 39Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

40. 40Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

41. 41Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

42. 42Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, the Netherlands.

43. 43Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.

44. 44Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.

45. 45Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

46. 46Biomedical Center, Faculty of Medicine Pilsen, Charles University, Prague, Czech Republic.

47. 47Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

48. 48Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.

49. 49Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York.

Abstract

AbstractBackground:Polygenic risk scores (PRS) which summarize individuals’ genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.Methods:The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).Results:In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91–1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71–0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.Conclusions:The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.Impact:The proposed model has potential utility in risk-stratified colorectal cancer prevention.

Funder

National Institutes of Health

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

Link

https://aacrjournals.org/cebp/article-pdf/doi/10.1158/1055-9965.EPI-22-0817/3239212/epi-22-0817.pdf

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