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ARTICLE

C-Reactive Protein Levels Are Not Associated with Increased Risk for Colorectal Cancer in Women

Shumin M. Zhang, MD, ScD; Julie E. Buring, ScD; I-Min Lee, MBBS, ScD; Nancy R. Cook, ScD; and Paul M. Ridker, MD, MPH

15 March 2005 | Volume 142 Issue 6 | Pages 425-432

Background: Observations that risk for colorectal cancer is elevated in patients with inflammatory bowel disease and that long-term use of anti-inflammatory drugs may reduce colorectal cancer risk have raised the possibility that inflammation may play a role in the development of colorectal cancer. While a recent prospective study observed a positive association between C-reactive protein (CRP), a marker of inflammation, and risk for colon cancer, data testing this hypothesis are sparse.

Objective: To evaluate whether plasma CRP levels predict colorectal cancer risk in women.

Design: Prospective cohort study, with 97% morbidity follow-up and 100% mortality follow-up within the past 2 years.

Setting: Women's Health Study.

Participants: 27 913 apparently healthy women age 45 years or older who had CRP measured at entry into a trial of low-dose aspirin and vitamin E. Maximum length of intervention and follow-up was 10.8 years.

Measurements: Self-reported incident colorectal adenocarcinoma confirmed by medical record review.

Results: 169 women developed colorectal adenocarcinomas during follow-up. Baseline CRP levels were not significantly associated with colorectal cancer risk. The multivariate hazard ratios according to cutoff points for CRP proposed in clinical guidelines were 0.79 (95% CI, 0.53 to 1.17) for the category of 1 to 3 mg/L and 0.66 (CI, 0.43 to 1.03) for the category of greater than 3 mg/L (P for trend = 0.09), as compared with the category of less than 1 mg/L. High CRP levels were also not associated with increased risk in analyses done according to tumor location and stage at diagnosis, according to alternative cutoff points for CRP, or in any of the subgroups evaluated.

Limitations: Despite multivariate analysis, residual confounding might still be present. Although this study was prospective, we cannot completely exclude undetected cancer at baseline. Measurements for CRP were available for only 71% of women in the cohort; however, the women who did and those who did not provide blood were mostly similar.

Conclusions: Plasma CRP levels do not appear to predict an increased risk for developing colorectal cancer in apparently healthy women. Low-grade inflammation may not play an important role in increasing the risk for colorectal cancer.

Editors' Notes Context Some data suggest that low-grade inflammation may play a role in the development of colorectal cancer. Contribution In this 10-year prospective study involving 27 913 healthy women age 45 years or older, elevated C-reactive protein (CRP) levels at baseline were not associated with a higher likelihood of colorectal cancer. Cautions A single baseline CRP measurement may be an imperfect marker of inflammation. The investigators relied on a woman's report of cancer rather than an ongoing surveillance protocol for colorectal lesions. Implications Low-grade inflammation may not be associated with in-creased colorectal cancer risk. –The Editors

 

Author and Article Information

From Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts.

Acknowledgments: The authors thank Marilyn Chown for her statistical analytic support, the staff of the Women's Health Study, and the 39 876 dedicated participants of the Women's Health Study.

Grant Support: By research grants CA-47988 and HL-43851 from the National Institutes of Health, with additional support from the Doris Duke Foundation and the Donald W. Reynolds Foundation. Dr. Zhang is supported in part by a National Cancer Institute Career Development Award (CA096619).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Shumin M. Zhang, MD, ScD, Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215; e-mail, shumin.zhang{at}channing.harvard.edu.

Current Author Addresses: Drs. Zhang, Buring, Cook, Lee, and Ridker: Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215.

Author Contributions: Conception and design: S.M. Zhang, P.M. Ridker.

Analysis and interpretation of the data: S.M. Zhang, N.R. Cook, P.M. Ridker.

Drafting of the article: S.M. Zhang, P.M. Ridker.

Critical revision of the article for important intellectual content: S.M. Zhang, J.E. Buring, I.-M. Lee, N.R. Cook, P.M. Ridker.

Final approval of the article: S.M. Zhang, J.E. Buring, I.-M. Lee, N.R. Cook, P.M. Ridker.

Statistical expertise: S.M. Zhang, N.R. Cook, P.M. Ridker.

Obtaining of funding: J.E. Buring, P.M. Ridker.

Administrative, technical, or logistic support: S.M. Zhang, I.-M. Lee, P.M. Ridker.

Collection and assembly of data: S.M. Zhang, J.E. Buring, I.-M. Lee, P.M. Ridker.

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