Auto-antibodies to p53 and the subsequent development of colorectal cancer in a United States prospective cohort consortium

Colorectal Cancer

Cancer Epidemiol Biomarkers Prev. 2020 Sep 24:cebp.0780.2020. doi: 10.1158/1055-9965.EPI-20-0780. Online ahead of print.


BACKGROUND: Auto-antibodies to tumor suppressor p53 are found in a subset of colorectal cancer (CRC) patients. A recent prospective study in the US has reported a significant 1.8-fold increased odds for CRC development with pre-diagnostic sero-positivity to p53. In the present study, we sought to examine this association in a US CRC cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for CRC.

METHODS: Auto-antibodies to p53 were measured in pre-diagnostic blood samples of 3,702 incident CRC cases and 3,702 controls, matched by age, race, and sex, from 9 US prospective cohorts. The association of sero-positivity to p53 with CRC 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 sero-positive to p53, resulting in a statistically significant 33% increased CRC risk (OR: 1.33; 95% CI: 1.09, 1.61). By follow-up time, the association was only significant with CRC 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 pre-diagnostic sero-positivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing CRC within 4 years after blood draw.

IMPACT: Our finding suggests that p53 sero-positivity may not be a useful predictor of long-term CRC risk, however, it might be considered as a marker to aid in the early diagnosis of CRC.