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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium

Julia Butt, William J. Blot, Kala Visvanathan, Loïc Le Marchand, Lynne R. Wilkens, Yu Chen, Howard D. Sesso, Lauren Teras, Marc D. Ryser, Terry Hyslop, Sylvia Wassertheil-Smoller, Lesley F. Tinker, John D. Potter, Mingyang Song, Sonja I. Berndt, Tim Waterboer, Michael Pawlita and Meira Epplein
Julia Butt
1Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina.
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  • For correspondence: j.butt@dkfz-heidelberg.de
William J. Blot
3Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee.
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Kala Visvanathan
4Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
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Loïc Le Marchand
5Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawaii.
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Lynne R. Wilkens
5Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawaii.
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Yu Chen
6Department of Population Health, New York University School of Medicine, New York, New York.
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Howard D. Sesso
7Brigham and Women's Hospital, Boston, Massachusetts.
8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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Lauren Teras
9Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
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Marc D. Ryser
10Department of Population Health Sciences, and Department of Mathematics, Duke University, Durham, North Carolina.
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Terry Hyslop
2Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina.
11Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.
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Sylvia Wassertheil-Smoller
12Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York.
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Lesley F. Tinker
13Cancer Prevention Program, Division of Public Health Sciences at Fred Hutchinson Cancer Research Center, Seattle, Washington.
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John D. Potter
14Centre for Public Health Research, Massey University, Wellington, New Zealand.
15Fred Hutchinson Cancer Research Center, Seattle, Washington.
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Mingyang Song
8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
16Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
17Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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Sonja I. Berndt
18Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
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Tim Waterboer
1Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Michael Pawlita
1Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Meira Epplein
2Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina.
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DOI: 10.1158/1055-9965.EPI-20-0780 Published December 2020
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Abstract

Background: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer.

Methods: Auto-antibodies to p53 were measured in prediagnostic blood samples of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression.

Results: Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.09–1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27; 95% CI, 1.62–3.19), but not thereafter (OR, 0.97; 95% CI, 0.76–1.24).

Conclusions: In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw.

Impact: Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk; however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Cancer Epidemiol Biomarkers Prev 2020;29:2729–34

  • Received May 20, 2020.
  • Revision received August 1, 2020.
  • Accepted September 21, 2020.
  • Published first September 24, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 29 (12)
December 2020
Volume 29, Issue 12
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Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium
Julia Butt, William J. Blot, Kala Visvanathan, Loïc Le Marchand, Lynne R. Wilkens, Yu Chen, Howard D. Sesso, Lauren Teras, Marc D. Ryser, Terry Hyslop, Sylvia Wassertheil-Smoller, Lesley F. Tinker, John D. Potter, Mingyang Song, Sonja I. Berndt, Tim Waterboer, Michael Pawlita and Meira Epplein
Cancer Epidemiol Biomarkers Prev December 1 2020 (29) (12) 2729-2734; DOI: 10.1158/1055-9965.EPI-20-0780

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Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium
Julia Butt, William J. Blot, Kala Visvanathan, Loïc Le Marchand, Lynne R. Wilkens, Yu Chen, Howard D. Sesso, Lauren Teras, Marc D. Ryser, Terry Hyslop, Sylvia Wassertheil-Smoller, Lesley F. Tinker, John D. Potter, Mingyang Song, Sonja I. Berndt, Tim Waterboer, Michael Pawlita and Meira Epplein
Cancer Epidemiol Biomarkers Prev December 1 2020 (29) (12) 2729-2734; DOI: 10.1158/1055-9965.EPI-20-0780
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