Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Prevention Research
Cancer Prevention Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Research Article

C-reactive Protein and Risk of Colorectal Adenoma According to Celecoxib Treatment

Andrew T. Chan, Camelia S. Sima, Ann G. Zauber, Paul M. Ridker, Ernest T. Hawk and Monica M. Bertagnolli
Andrew T. Chan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Camelia S. Sima
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ann G. Zauber
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul M. Ridker
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ernest T. Hawk
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Monica M. Bertagnolli
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1940-6207.CAPR-10-0403 Published August 2011
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

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. Cancer Prev Res; 4(8); 1172–80. ©2011 AACR.

See perspective on p. 1145

Introduction

Aspirin and selective COX-2 inhibitors, such as celecoxib, reduce risk of colorectal adenoma and cancer (1–5). This effect may be mediated through abrogation of inflammation (6–8). High-sensitivity C-reactive protein (hsCRP) is a circulating inflammatory biomarker of chronic conditions including cardiovascular disease (9, 10). However, prospective studies relating hsCRP to risk of colorectal cancer and adenoma have been equivocal (11–29).

In the Adenoma Prevention with Celecoxib (APC) trial, patients who had recently undergone colonoscopic removal of an adenoma were randomly assigned to receive placebo, 200 mg twice daily (200-mg-bid) of celecoxib, or 400 mg twice daily (400-mg-bid) of celecoxib and underwent follow-up colonoscopies at 1 and 3 years. The relative risk (RR) of the detection of 1 or more new adenomas by year 3 compared with placebo was 0.67 (95% CI = 0.59–0.77) for those receiving 200-mg-bid celecoxib and 0.55 (95% CI = 0.48–0.64) for those receiving 400-mg-bid celecoxib (4). Unfortunately, in a separate, adjudicated safety analysis, the APC trial also revealed unexpected dose-related cardiovascular toxicity (30). Because hsCRP may be related to both risk of neoplasia and cardiovascular events and celecoxib has been shown to reduce hsCRP levels (31, 32), we examined baseline hsCRP in relation to (i) risk of recurrent adenoma, (ii) celecoxib-related chemopreventive efficacy, and (iii) celecoxib-related cardiovascular toxicity.

Methods

Study population

Jointly sponsored by the National Cancer Institute and Pfizer, Inc., the APC trial was a randomized, placebo-controlled trial which enrolled patients within 6 months of colonoscopic removal of multiple adenomas or a single adenoma larger than 5 mm in diameter (ClinicalTrials.gov NCT00005094; ref. 4). Beginning in November 1999, 2,457 potential participants at 91 clinical sites were entered into a 30-day placebo run-in period during which they were required to have at least 80% adherence to medication use. After the run-in period, 2,035 patients were subsequently randomly assigned to placebo, 200-mg-bid of celecoxib, or 400-mg-bid of celecoxib. Randomization was stratified on the basis of the use or nonuse of low-dose aspirin (≤325 mg every other day or ≤162.5 mg every day) and clinical site. For the duration of the study, patients were required to abstain from long-term use of non–steroidal anti-inflammatory drugs. Patients were excluded if they had a history of familial adenomatous polyposis, hereditary nonpolyposis colon cancer, inflammatory bowel disease, or large-bowel resection other than appendectomy. Other exclusion criteria included a history of a renal or hepatic disorder, a clinically significant bleeding disorder, or treatment for a gastrointestinal ulcer before study entry. Study drug treatment was initially planned for 3 years for all participants. However, at the recommendation of the APC trial Data Safety Monitoring Board (DSMB), treatment was terminated prematurely on December 17, 2004, based on the results of an unscheduled safety analysis conducted by an independent cardiovascular safety committee. At that time 1,762 patients (86.6%) had completed 3 years of treatment and 273 patients had 1 to 3 months of treatment remaining. In addition, 639 patients had begun participation in the extension study in which study medication was continued in a blinded manner for an additional 2 years. The median duration of treatment exposure in the extension study was 3.5 years (33). All patients provided written informed consent and the human subjects committee at each site approved the study. This analysis was approved by the Human Subjects Committee of Partners HealthCare.

hsCRP measurements

At baseline randomization, 1,707 participants provided a serum specimen at baseline randomization which was subsequently stored at −70°C. Personnel blinded to quality control and outcome data assayed for hsCRP using a high-sensitivity, latex-enhanced immunoturbidimetric assay (intra-assay coefficient of variation = 2.9%; Denka Seiken). Among the 1,707 specimens, 27 could not be measured for technical reasons (Fig. 1). Thus, this analysis included 1,680 participants, which were similar according to baseline characteristics to those for whom we did not measure hsCRP (data not shown).

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Flow of patients through the study. Patients who violated study entry criteria were those for whom the presence or absence of adenoma on the baseline colonoscopy could not be confirmed. Adherence to the use of study medication was calculated as duration of use in days, divided by 1,095.

Outcome ascertainment

A study investigator conducted follow-up colonoscopies with endoscopic removal of polyps at 1 and 3 years after randomization. A central study pathologist examined, in a blinded fashion, all polyps removed during these colonoscopies. Adverse events were reported by investigators and classified according to criteria from the Medical Dictionary for Regulatory Activities (MedDRA), version 8.1 (4, 33).

Statistical analysis

As in prior studies (21), we examined hsCRP levels according to cutoff points proposed in clinical guidelines (<1, 1–3, and >3 mg/L; ref. 34). Consistent with the intent-to-treat principle, we used the detection of an adenoma during a postrandomization colonoscopy, regardless of whether the patient adhered to the treatment regimen, as the primary endpoint. We estimated the cumulative incidence of adenoma at 3 years within different subgroups using Kaplan–Meier method. The effect of hsCRP levels on having a recurrent adenoma at a postrandomization colonoscopy was estimated by RR derived from Cox proportional hazards modeling with ties handled by the exact method, stratified by age (≥65 vs. <65), sex, time, baseline use of low-dose aspirin (≤325 mg/every other day or ≤162.5 mg/d), postmenopausal hormones, and duration of statin use (≤3 vs. >3 y) as a time-dependent variable (35). We used Cox proportional hazards models, adjusted for the same variables as the efficacy analyses, to estimate the RR of an investigator-reported adverse event after the first dose and up to 30 days after the last dose of study medication including events among patients who continued study medication in the 24-month extension study (33, 35). We used the SAS version 9.1 (SAS Institute) for all analyses. All significance tests were 2 sided at a 5% level of significance.

Results

Among the 1,680 participants, the median age was 59 [range = 31–88] years, 92% were white, and 68% were men, and the median hsCRP level was 1.6 mg/L (range = 0.1–2.72 mg/L). Patients with elevated CRP levels (>3 mg/L) more frequently smoked, had a higher body mass index, had a prior history of cardiovascular events, hypertension, and diabetes mellitus, and used low-dose aspirin and statin drugs. Consistent with the known effect of postmenopausal hormones on CRP levels (36), the prevalence of postmenopausal hormone use was higher among women with elevated CRP. The number of adenomas (P = 0.24) or adenoma burden (sum of diameter of all adenomas; P = 0.61) at the baseline qualifying examination did not vary according to hsCRP (Table 1).

View this table:
  • View inline
  • View popup
Table 1.

Baseline characteristics of the patients according to serum hsCRP levelsa

Baseline hsCRP was not statistically significantly associated with risk of recurrent colorectal adenoma. The RR of adenoma through year 3 associated with a 1 SD increase in log hsCRP was 0.96 (95% CI = 0.89–1.03). The estimated 3-year cumulative incidence of adenoma was 42% for patients with hsCRP <1 mg/L, compared with 43% (RR = 1.02; 95% CI = 0.85–1.22) for hsCRP 1–3 mg/L, and 41% (RR = 1.1; 95% CI = 0.90–1.34) for hsCRP >3 mg/L. These results did not vary according to strata defined by celecoxib assignment, aspirin use, sex, use of postmenopausal hormones, body mass index, or use of statin drugs (Table 2). When we analyzed data according to quartile cutoff points of the distribution of hsCRP, our results were essentially unchanged (data not shown). We also examined hsCRP in relation to risk of advanced adenoma. The estimated 3-year cumulative incidence of advanced adenoma was 8.2% for patients with hsCRP <1 mg/L, compared with 7.5% (RR = 0.90; 95% CI = 0.59–1.38) for hsCRP 1–3 mg/L, and 5.6% (RR = 0.72; 95% CI = 0.44–1.17) for hsCRP >3 mg/L.

View this table:
  • View inline
  • View popup
Table 2.

Risk of adenoma according to serum hsCRP levels

The overall reduction in cumulative incidence of adenoma associated with celecoxib did not appear to vary among patients with high (>3 mg/L) compared with low (≤3 mg/L) hsCRP (Table 3). 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; Table 4; Fig. 2). A formal test of interaction between high hsCRP and 400-mg-bid celecoxib approached statistical significance (P = 0.11). We considered the possibility that concurrent aspirin use may modify the interaction between high hsCRP levels and celecoxib-associated cardiovascular events. Among patients with hsCRP >3 mg/L and were not taking low-dose aspirin, the RR for a cardiovascular event compared to those randomized to placebo was 2.74 (95% CI = 0.54–13.70) for those randomized to celecoxib 200-mg-bid and 4.98 (95% CI = 1.10–22.59) for those randomized to celecoxib 400-mg-bid. In contrast, among patients with hsCRP >3 mg/L and were taking low-dose aspirin, the RR for a cardiovascular event compared with those randomized to placebo was 1.72 (95% CI = 0.33–8.96) for those randomized to celecoxib 200-mg-bid, and 1.65 (95% CI = 0.30–9.0) for those randomized to celecoxib 400-mg-bid. Although these results do suggest a possible attenuation of cardiovascular risk associated with low-dose aspirin, a formal test of interaction between celecoxib treatment and use of low-dose aspirin was not statistically significant (P = 0.57). Moreover, because there were limited numbers of events within each aspirin strata (19 events in the group not taking aspirin and 12 events in the group taking low-dose aspirin), these results should be considered exploratory. Finally, among all patients, there did not appear to be an overall dose-related increase in either renal and hypertensive disorders or gastrointestinal ulceration and hemorrhage, consistent with the overall results of the trial (4).

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Relative risk of cardiovascular events according to baseline hsCRP. Error bars correspond to 95% CIs.

View this table:
  • View inline
  • View popup
Table 3.

Risk of adenoma according to celecoxib treatment, stratified by hsCRP levela

View this table:
  • View inline
  • View popup
Table 4.

Risk of adverse events according to celecoxib treatment, stratified by hsCRP levela

Discussion

The divergent results of previous studies relating hsCRP to colorectal adenoma or cancer may be related to the timing at which hsCRP was measured (11–29). Specifically, positive studies may reflect hsCRP elevations associated with occult disease including adenoma (11, 12, 14, 22). In support of this explanation, cross-sectional data measuring hsCRP at the time of colonoscopy have shown a modest association with prevalent adenoma (24, 25), whereas a prospective study of incident adenoma and a cross-sectional study measuring hsCRP several years before diagnosis of adenoma showed inverse or no association (26, 28). In our study, because we examined hsCRP levels among individuals within 6 months of a clearing colonoscopy and endpoints were ascertained at protocol-defined surveillance colonoscopies, our results more closely reflect the association between hsCRP and incident neoplasia. Our findings are largely consistent with those of the similarly designed Aspirin Polyp Prevention Study (PPS; ref. 37). However, the results from both the APC and Aspirin PPS trials do not exclude a potential association between hsCRP and the initial development of adenoma rather than recurrence. A limitation of our study is that we only had a single baseline measure of hsCRP and we could not correlate change in hsCRP with celecoxib treatment. However, celecoxib treatment reduced adenoma recurrence irrespective of baseline levels of hsCRP. Taken together with data from the Aspirin PPS which did measure hsCRP levels at baseline and at year 3, our findings support the conclusion that hsCRP does not mediate the chemopreventive effect of aspirin or celecoxib (37).

Among individuals with high hsCRP levels (>3 mg/L), celecoxib treatment was associated with a 3-fold higher risk of an adverse cardiovascular event; in contrast, among those with low hsCRP (≤3 mg/L), celecoxib treatment was not associated with higher risk. Although a formal test for interaction was not significant, this is likely due to the limited number of adverse cardiovascular events. These findings are consistent with emerging data that individuals can be stratified for celecoxib cardiovascular toxicity according to baseline cardiovascular risk. A prior pooled analysis of 6 placebo-controlled trials of celecoxib observed that patients with high baseline cardiovascular risk scores had the greatest risk of celecoxib-related adverse events (38). Similarly, a 5-year safety analysis of an extension of the APC trial showed a significant interaction between a baseline history of atherosclerotic heart disease and risk of celecoxib-associated cardiovascular events (33). Further studies are needed to determine whether baseline hsCRP alone can be used to identify patients for whom long-term use of celecoxib is relatively safe.

In the APC trial, patients were randomized to either 200-mg-bid or 400-mg-bid doses of celecoxib. Thus, it is unclear if baseline hsCRP may also predict risk of cardiovascular events among patients who take celecoxib once daily. In a parallel randomized, placebo-controlled trial, treatment with 400 mg of daily celecoxib was associated with an overall nonsignificant increase in risk of cardiovascular events (RR = 1.30; 95% CI = 0.65–2.62; ref. 5). Thus, it is possible that use of a once daily dosing of celecoxib among patients with low hsCRP may be a particularly effective strategy to minimize cardiovascular risk.

Finally, in our analysis, we did observe a nonsignificant increase in risk of renal and hypertensive events in the subgroup of patients with low hsCRP randomized to 200-mg-bid. In contrast, there was no association among those randomized to 400-mg-bid. On the basis of this lack of a dose response, it is unlikely that there is a unique biological interaction between celecoxib and low baseline inflammatory state and renal or hypertensive events. Nonetheless, larger studies with a greater number of such endpoints are needed to make definitive conclusions.

In this large, randomized, placebo-controlled trial, baseline hsCRP was not associated with overall risk of adenoma recurrence or celecoxib chemopreventive benefit after 3 years of treatment. However, individuals with high hsCRP appeared to have the greatest risk of celecoxib-related cardiovascular toxicity. Further studies are needed to determine the role of hsCRP in relation to other markers of cardiovascular risk to evaluate the risk-benefit profile of celecoxib treatment for a range of clinical indications.

Disclosure of Potential Conflicts of Interest

A.T. Chan is a Damon Runyon Cancer Research Foundation Clinical Investigator and has served as a consultant to Bayer HealthCare. M.M. Bertagnolli is the recipient of research funding from Pfizer Inc. E.T. Hawk has served as a consultant for Pozen Pharmaceutical Development Company. P.M. Ridker is listed as a coinventor on patents held by Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes that have been licensed to Siemens and AstraZeneca. C.S. Sima has no conflicts of interest. The statistical analysis of the entire data sets pertaining to efficacy and safety has been independently confirmed by A.G. Zauber, who is not employed by any corporate entity. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and analysis.

Grant Support

This work was supported by the National Cancer Institute at the NIH (grant number R01 CA137178 to A.T. Chan and N01 CN95015 to M.M. Bertagnolli).

Acknowledgments

The authors thank Dr. Nader Rifai and Mr. Gary Bradwin for technical assistance with the CRP assays.

Footnotes

  • Note: Portions of this data were previously presented in abstract form at Digestive Disease Week in Chicago, IL, on May 30–June 4, 2009.

  • Received December 30, 2010.
  • Revision received February 18, 2011.
  • Accepted March 29, 2011.
  • ©2011 American Association for Cancer Research.

References

  1. 1.↵
    1. Chan AT,
    2. Ogino S,
    3. Fuchs CS
    . Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 2007;356:2131–42.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Baron JA,
    2. Cole BF,
    3. Sandler RS,
    4. Haile RW,
    5. Ahnen D,
    6. Bresalier R,
    7. et al.
    A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891–9.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Cole BF,
    2. Logan RF,
    3. Halabi S,
    4. Benamouzig R,
    5. Sandler RS,
    6. Grainge MJ,
    7. et al.
    Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 2009;101:256–66.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Bertagnolli MM,
    2. Eagle CJ,
    3. Zauber AG,
    4. Redston M,
    5. Solomon SD,
    6. Kim K,
    7. et al.
    Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 2006;355:873–84.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Arber N,
    2. Eagle CJ,
    3. Spicak J,
    4. Rácz I,
    5. Dite P,
    6. Hajer J,
    7. et al.
    Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 2006;355:885–95.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Schottenfeld D,
    2. Beebe-Dimmer J
    . Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin 2006;56:69–83.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Balkwill F,
    2. Mantovani A
    . Inflammation and cancer: back to Virchow? Lancet 2001;357:539–45.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Shacter E,
    2. Weitzman SA
    . Chronic inflammation and cancer. Oncology 2002;16:217–26, 229; discussion 230–2.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Ridker PM,
    2. Cushman M,
    3. Stampfer MJ,
    4. Tracy RP,
    5. Hennekens CH
    . Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973–9.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Ridker PM,
    2. Hennekens CH,
    3. Buring JE,
    4. Rifai N
    . C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836–43.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Erlinger TP,
    2. Platz EA,
    3. Rifai N,
    4. Helzlsouer KJ
    . C-reactive protein and the risk of incident colorectal cancer. JAMA 2004;291:585–90.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Il'yasova D,
    2. Colbert LH,
    3. Harris TB,
    4. Newman AB,
    5. Bauer DC,
    6. Satterfield S,
    7. et al.
    Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort. Cancer Epidemiol Biomarkers Prev 2005;14:2413–8.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Ito Y,
    2. Suzuki K,
    3. Tamakoshi K,
    4. Wakai K,
    5. Kojima M,
    6. Ozasa K,
    7. et al.
    Colorectal cancer and serum C-reactive protein levels: a case-control study nested in the JACC Study. J Epidemiol 2005;15Suppl 2:S185–9.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Gunter MJ,
    2. Stolzenberg-Solomon R,
    3. Cross AJ,
    4. Leitzmann MF,
    5. Weinstein S,
    6. Wood RJ,
    7. et al.
    A prospective study of serum C-reactive protein and colorectal cancer risk in men. Cancer Res 2006;66:2483–7.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. Otani T,
    2. Iwasaki M,
    3. Sasazuki S,
    4. Inoue M,
    5. Tsugane S
    . Plasma C-reactive protein and risk of colorectal cancer in a nested case-control study: Japan Public Health Center-based prospective study. Cancer Epidemiol Biomarkers Prev 2006;15:690–5.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Trichopoulos D,
    2. Psaltopoulou T,
    3. Orfanos P,
    4. Trichopoulou A,
    5. Boffetta P
    . Plasma C-reactive protein and risk of cancer: a prospective study from Greece. Cancer Epidemiol Biomarkers Prev 2006;15:381–4.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Siemes C,
    2. Visser LE,
    3. Coebergh JW,
    4. Splinter TA,
    5. Witteman JC,
    6. Uitterlinden AG,
    7. et al.
    C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol 2006;24:5216–22.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Heikkilä K,
    2. Harris R,
    3. Lowe G,
    4. Rumley A,
    5. Yarnell J,
    6. Gallacher J,
    7. et al.
    Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control 2009;20:15–26.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Allin KH,
    2. Bojesen SE,
    3. Nordestgaard BG
    . Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 2009;27:2217–24.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Allin KH,
    2. Nordestgaard BG,
    3. Zacho J,
    4. Tybjaerg-Hansen A,
    5. Bojesen SE
    . C-reactive protein and the risk of cancer: a mendelian randomization study. J Natl Cancer Inst 2010;102:202–6.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Zhang SM,
    2. Buring JE,
    3. Lee IM,
    4. Cook NR,
    5. Ridker PM
    . C-reactive protein levels are not associated with increased risk for colorectal cancer in women. Ann Intern Med 2005;142:425–32.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Aleksandrova K,
    2. Jenab M,
    3. Boeing H,
    4. Jansen E,
    5. Bueno-de-Mesquita HB,
    6. Rinaldi S,
    7. et al.
    Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol 2010;172:407–18.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    1. Chan AT,
    2. Ogino S,
    3. Giovannucci EL,
    4. Fuchs CS
    . Inflammatory markers are associated with risk of colorectal cancer and chemopreventive response to anti-inflammatory drugs. Gastroenterology 2011;140:799–808.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Otake T,
    2. Uezono K,
    3. Takahashi R,
    4. Fukumoto J,
    5. Tabata S,
    6. Abe H,
    7. et al.
    C-reactive protein and colorectal adenomas: Self Defense Forces Health Study. Cancer Sci 2009;100:709–14.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Kim S,
    2. Keku TO,
    3. Martin C,
    4. Galanko J,
    5. Woosley JT,
    6. Schroeder JC,
    7. et al.
    Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 2008;68:323–8.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    1. Tsilidis KK,
    2. Erlinger TP,
    3. Rifai N,
    4. Hoffman S,
    5. Hoffman-Bolton J,
    6. Helzlsouer KJ,
    7. et al.
    C-reactive protein and colorectal adenoma in the CLUE II cohort. Cancer Causes Control 2008;19:559–67.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Ognjanovic S,
    2. Yamamoto J,
    3. Saltzman B,
    4. Franke A,
    5. Ognjanovic M,
    6. Yokochi L,
    7. et al.
    Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population. Cancer Causes Control 2010;21:1131–8.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Gunter MJ,
    2. Cross AJ,
    3. Huang WY,
    4. Stanczyk FZ,
    5. Purdue M,
    6. Xue X,
    7. et al.
    A prospective evaluation of C-reactive protein levels and colorectal adenoma development. Cancer Epidemiol Biomarkers Prev 2011;20:537–44.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Prizment AE,
    2. Anderson KE,
    3. Visvanathan K,
    4. Folsom AR
    . Association of inflammatory markers with colorectal cancer incidence in the atherosclerosis risk in communities study. Cancer Epidemiol Biomarkers Prev 2011;20:297–307.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Solomon SD,
    2. McMurray JJ,
    3. Pfeffer MA,
    4. Wittes J,
    5. Fowler R,
    6. Finn P,
    7. et al.
    Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1071–80.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Chenevard R,
    2. Hürlimann D,
    3. Béchir M,
    4. Enseleit F,
    5. Spieker L,
    6. Hermann M,
    7. et al.
    Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation 2003;107:405–9.
    OpenUrlAbstract/FREE Full Text
  32. 32.↵
    1. Bogaty P,
    2. Brophy JM,
    3. Noel M,
    4. Boyer L,
    5. Simard S,
    6. Bertrand F,
    7. et al.
    Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study. Circulation 2004;110:934–9.
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    1. Bertagnolli MM,
    2. Eagle CJ,
    3. Zauber AG,
    4. Redston M,
    5. Breazna A,
    6. Kim K,
    7. et al.
    Five-year efficacy and safety analysis of the Adenoma Prevention with Celecoxib Trial. Cancer Prev Res 2009;2:310–21.
    OpenUrlAbstract/FREE Full Text
  34. 34.↵
    1. Pearson TA,
    2. Mensah GA,
    3. Alexander RW,
    4. Anderson JL,
    5. Cannon RO,
    6. Criqui M,
    7. et al.
    Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499–511.
    OpenUrlFREE Full Text
  35. 35.↵
    1. Chan AT,
    2. Zauber AG,
    3. Hsu M,
    4. Breazna A,
    5. Hunter DJ,
    6. Rosenstein RB,
    7. et al.
    Cytochrome P450 2C9 variants influence response to celecoxib for prevention of colorectal adenoma. Gastroenterology 2009;136:2127–36e1.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Ridker PM,
    2. Hennekens CH,
    3. Rifai N,
    4. Buring JE,
    5. Manson JE
    . Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999;100:713–6.
    OpenUrlAbstract/FREE Full Text
  37. 37.↵
    1. Ho GY,
    2. Xue X,
    3. Cushman M,
    4. McKeown-Eyssen G,
    5. Sandler RS,
    6. Ahnen DJ,
    7. et al.
    Antagonistic effects of aspirin and folic acid on inflammation markers and subsequent risk of recurrent colorectal adenomas. J Natl Cancer Inst 2009;101:1650–4.
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    1. Solomon SD,
    2. Wittes J,
    3. Finn PV,
    4. Fowler R,
    5. Viner J,
    6. Bertagnolli MM,
    7. et al.
    Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 2008;117:2104–13.
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Cancer Prevention Research: 4 (8)
August 2011
Volume 4, Issue 8
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Prevention Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
C-reactive Protein and Risk of Colorectal Adenoma According to Celecoxib Treatment
(Your Name) has forwarded a page to you from Cancer Prevention Research
(Your Name) thought you would be interested in this article in Cancer Prevention Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
C-reactive Protein and Risk of Colorectal Adenoma According to Celecoxib Treatment
Andrew T. Chan, Camelia S. Sima, Ann G. Zauber, Paul M. Ridker, Ernest T. Hawk and Monica M. Bertagnolli
Cancer Prev Res August 1 2011 (4) (8) 1172-1180; DOI: 10.1158/1940-6207.CAPR-10-0403

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
C-reactive Protein and Risk of Colorectal Adenoma According to Celecoxib Treatment
Andrew T. Chan, Camelia S. Sima, Ann G. Zauber, Paul M. Ridker, Ernest T. Hawk and Monica M. Bertagnolli
Cancer Prev Res August 1 2011 (4) (8) 1172-1180; DOI: 10.1158/1940-6207.CAPR-10-0403
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Grant Support
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Obesity and Telomere Length in Prostate Stromal Cells
  • Regulatory T Cells and Melanocytic Nevi
  • mt-sDNA Specificity in 45–49 Year-Olds
Show more Research Articles
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Prevention Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Prevention Research
eISSN: 1940-6215
ISSN: 1940-6207

Advertisement