C-reactive protein and risk of colorectal adenoma according to celecoxib treatment Journal Article

Authors: Chan, A. T.; Sima, C. S.; Zauber, A. G.; Ridker, P. M.; Hawk, E. T.; Bertagnolli, M. M.
Article Title: C-reactive protein and risk of colorectal adenoma according to celecoxib treatment
Abstract: Inflammation, as measured by the circulating inflammatory marker high-sensitivity C-reactive protein (hsCRP), has been associated with cardiovascular disease. However, data about CRP and risk of colorectal cancer have been conflicting. The Adenoma Prevention with Celecoxib (APC) trial showed that the antiinflammatory drug celecoxib prevents recurrence of colorectal adenoma but increases risk of cardiovascular events. We examined whether serum hsCRP modified these results. We measured hsCRP from serum specimens provided at study entry by patients enrolled in the APC trial. Patients were stratified according to use of low-dose aspirin, randomized to receive 3 years of treatment with placebo, 200-mg-bid celecoxib, or 400-mg-bid celecoxib, and underwent follow-up colonoscopies at years 1 and 3. Among 1,680 patients, the estimated 3-year cumulative incidence of adenoma was 42% for patients with hsCRP <1 mg/L, compared with 43% [relative risk (RR) = 1.02; 95% CI = 0.85-1.22] for hsCRP 1-3 mg/L, and 41% (RR = 1.10; 95% CI = 0.90-1.34) for hsCRP >3 mg/L. The effect of celecoxib on adenoma recurrence did not vary among patients with high (>3 mg/L) compared with low (≤3 mg/L) hsCRP. However, among patients with high hsCRP, the RR of cardiovascular events compared with placebo was 2.27 (95% CI = 0.72-7.14) for those randomized to celecoxib 200-mg-bid and 3.28 (95% CI = 1.09-9.91) for 400-mg-bid. In contrast, among patients with low hsCRP, the corresponding RRs were 0.99 (95% CI = 0.53-1.83) and 1.11 (95% CI = 0.61-2.02). hsCRP may predict risk of celecoxib-associated cardiovascular toxicity but not adenoma recurrence or celecoxib treatment efficacy. Patients with low hsCRP may be a subgroup with a favorable risk-benefit profile for celecoxib chemoprevention. ©2011 AACR.
Keywords: adult; controlled study; aged; aged, 80 and over; middle aged; major clinical study; cancer recurrence; placebo; cancer risk; drug efficacy; follow up; cancer incidence; c reactive protein; cancer prevention; low drug dose; randomized controlled trial; inflammation; recurrence; c-reactive protein; drug effect; risk factor; risk; colorectal neoplasms; adenoma; acetylsalicylic acid; celecoxib; cardiovascular risk; colonoscopy; colorectal adenoma; cardiovascular diseases; pyrazoles; sulfonamides; cardiotoxicity; anticarcinogenic agents; double blind procedure; placebos
Journal Title: Cancer Prevention Research
Volume: 4
Issue: 8
ISSN: 1940-6207
Publisher: American Association for Cancer Research  
Date Published: 2011-08-01
Start Page: 1172
End Page: 1180
Language: English
DOI: 10.1158/1940-6207.capr-10-0403
PUBMED: 21816845
PROVIDER: scopus
PMCID: PMC3151679
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 7 June 2012" - "Source: Scopus"
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MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Ann G Zauber
    218 Zauber