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 anti-inflammatory 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.
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. achan@partners.org
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Ann G
authors.initials: AG
authors.lastname: Zauber
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Hawk
authors.forename: Monica M
authors.initials: MM
authors.lastname: Bertagnolli
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000096:biosynthesis*; D002318:Cardiovascular Diseases / Q000209:etiology; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D012008:Recurrence; D012306:Risk; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D002097:C-Reactive Protein; D000068579:Celecoxib