TY - JOUR
T1 - Auto-antibodies to p53 and the subsequent development of colorectal cancer in a U.S. Prospective Cohort Consortium
AU - Butt, Julia
AU - Blot, William J.
AU - Visvanathan, Kala
AU - Le Marchand, Loïc
AU - Wilkens, Lynne R.
AU - Chen, Yu
AU - Sesso, Howard D.
AU - Teras, Lauren
AU - Ryser, Marc D.
AU - Hyslop, Terry
AU - Wassertheil-Smoller, Sylvia
AU - Tinker, Lesley F.
AU - Potter, John D.
AU - Song, Mingyang
AU - Berndt, Sonja I.
AU - Waterboer, Tim
AU - Pawlita, Michael
AU - Epplein, Meira
N1 - Funding Information:
W.J. Blot reports grants from NIH during the conduct of the study. K. Visvanathan reports grants from NIH during the conduct of the study. L. Le Marchand reports grants from NCI (to institution) during the conduct of the study. T. Hyslop reports grants from NCI during the conduct of the study, as well as personal fees from AbbVie (not oncology related) outside the submitted work. M. Epplein reports grants from NCI during the conduct of the study. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
The NCI, NIH, U.S. Department of Health and Human Services funds this consortium (R01 CA190428 to M. Epplein); the Southern Community Cohort Study (U01 CA202979 to W.J. Blot); the NYU Women’s Health Study (U01 CA182934 to Y. Chen); the MEC (U01 CA164973 to L. Le Marchand); the NHS/ HPFS (U01 CA167552, UM1 CA186107, P01 CA087969, and UM1CA167552); the PHS (R01 CA097193, R01 CA040360, and R01 HL034595); and R00 CA215314 to M. Song. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts, HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. CLUE thanks the participants
Funding Information:
The NCI, NIH, U.S. Department of Health and Human Services funds this consortium (R01 CA190428 to M. Epplein); the Southern Community Cohort Study (U01 CA202979 to W.J. Blot); the NYU Women's Health Study (U01 CA182934 to Y. Chen); the MEC (U01 CA164973 to L. Le Marchand); the NHS/ HPFS (U01 CA167552, UM1 CA186107, P01 CA087969, and UM1CA167552); the PHS (R01 CA097193, R01 CA040360, and R01 HL034595); and R00 CA215314 to M. Song. The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts, HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. CLUE thanks the participants and staff for their contributions, as well as the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene (http:// phpa.dhmh.maryland.gov/cancer).
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85100980635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100980635&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-20-0780
DO - 10.1158/1055-9965.EPI-20-0780
M3 - Review article
C2 - 32972968
AN - SCOPUS:85100980635
VL - 29
SP - 2729
EP - 2734
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 12
ER -