• Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. j.butt@dkfz-heidelberg.de.
• Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee.
• Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland.
• Epidemiology Program, University of Hawai'i Cancer Center, Honolulu, Hawaii.
• Department of Population Health, New York University School of Medicine, New York, New York.
• Brigham and Women's Hospital, Boston, Massachusetts.
• Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
• Department of Population Health Sciences, and Department of Mathematics, Duke University, Durham, North Carolina.
• Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina.
• Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, New York.

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.