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Original Research |

Alternate-Day, Low-Dose Aspirin and Cancer Risk: Long-Term Observational Follow-up of a Randomized Trial

Nancy R. Cook, ScD; I-Min Lee, ScD; Shumin M. Zhang, ScD; M. Vinayaga Moorthy, PhD; and Julie E. Buring, ScD
[+] Article and Author Information

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

Note: Aspirin and aspirin placebo were provided by Bayer HealthCare. Vitamin E and vitamin E placebo were provided by the Natural Source Vitamin E Association, Chicago, Illinois.

Grant Support: By grants HL043851, HL080467, HL099355, and CA047988 from the National Heart, Lung, and Blood Institute and the National Cancer Institute, Bethesda, Maryland.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-2816.

Reproducible Research Statement: Study protocol and statistical code: Available from the authors upon written request. Data set: Not available.

Requests for Single Reprints: Nancy R. Cook, ScD, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215; e-mail, ncook@rics.bwh.harvard.edu.

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

Author Contributions: Conception and design: N.R. Cook, I.M. Lee, S.M. Zhang, J.E. Buring.

Analysis and interpretation of the data: N.R. Cook, S.M. Zhang, M.V. Moorthy.

Drafting of the article: N.R. Cook.

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

Final approval of the article: N.R. Cook, I.M. Lee, S.M. Zhang, M.V. Moorthy, J.E. Buring.

Provision of study materials or patients: J.E. Buring.

Statistical expertise: N.R. Cook.

Obtaining of funding: I.M. Lee, S.M. Zhang, J.E. Buring.

Administrative, technical, or logistic support: I.M. Lee, J.E. Buring.

Collection and assembly of data: I.M. Lee, S.M. Zhang, M.V. Moorthy, J.E. Buring.


Ann Intern Med. 2013;159(2):77-85. doi:10.7326/0003-4819-159-2-201307160-00002
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Chinese translation

Background: Recent evidence suggests that daily aspirin use decreases cancer risk, particularly for colorectal cancer, but evidence for alternate-day use is scant.

Objective: To examine the association between long-term, alternate-day, low-dose aspirin and cancer in healthy women.

Design: Observational follow-up of a randomized trial.

Setting: Female health professionals.

Participants: 39 876 women aged 45 years or older in the Women's Health Study (ClinicalTrials.gov: NCT00000479), 33 682 of whom continued observational follow-up.

Intervention: 100 mg of alternate-day aspirin or placebo through March 2004, with a median 10-year follow-up. Posttrial follow-up continued through March 2012.

Measurements: Cancer incidence.

Results: A total of 5071 cancer cases (including 2070 breast, 451 colorectal, and 431 lung cancer cases) and 1391 cancer deaths were confirmed. Over the entire follow-up, aspirin had no association with total (hazard ratio [HR], 0.97 [95% CI, 0.92 to 1.03]; P = 0.31), breast (HR, 0.98 [CI, 0.90 to 1.07]; P = 0.65), or lung (HR, 1.04 [CI, 0.86 to 1.26]; P = 0.67) cancer. Colorectal cancer was reduced in the aspirin group (HR, 0.80 [CI, 0.67 to 0.97]; P = 0.021), primarily for proximal colon cancer (HR, 0.73 [CI, 0.55 to 0.95]; P = 0.022). The difference emerged after 10 years, with a posttrial reduction of 42% (HR, 0.58 [CI, 0.42 to 0.80]; P < 0.001). There was no extended effect on cancer deaths or colorectal polyps. More gastrointestinal bleeding (HR, 1.14 [CI, 1.06 to 1.22]; P < 0.001) and peptic ulcers (HR, 1.17 [CI, 1.09 to 1.27]; P < 0.001) occurred in the aspirin group.

Limitations: Not all women received extended follow-up, and posttrial ascertainment bias cannot be ruled out. Gastrointestinal bleeding, peptic ulcers, and polyps were self-reported during extended follow-up.

Conclusion: Long-term use of alternate-day, low-dose aspirin may reduce risk for colorectal cancer in healthy women.

Primary Funding Source: National Institutes of Health.

Topics

aspirin ; follow-up ; cancer

Figures

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Appendix Figure 1.

Use of at least two thirds of study pills (aspirin or placebo) and use of nonstudy aspirin for more than 3 d per month over years of follow-up, by random aspirin assignment.

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Figure 2.

Cumulative incidence of total(A), breast (B), colorectal (C), and lung (D) cancer from time of randomization, by random aspirin assignment, with P values from log-rank test.

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Appendix Figure 2.

Cumulative incidence of gastrointestinal cancer from time of randomization, by random aspirin assignment, withP value from log-rank test.

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Appendix Figure 3.

Cumulative incidence of metastatic cancer from time of randomization, by random aspirin assignment, withP value from log-rank test.

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Appendix Figure 4.

Cumulative incidence of adenocarcinoma from time of randomization, by random aspirin assignment, withP value from log-rank test.

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Appendix Figure 5.

Cumulative incidence of metastatic adenocarcinoma from time of randomization, by random aspirin assignment, withP value from log-rank test.

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Appendix Figure 6.

Cumulative incidence of gastrointestinal bleeding from time of randomization, by random aspirin assignment, withP value from log-rank test.

Irregularities over time are due to intermittent collection of these events after the trial.

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Appendix Figure 7.

Cumulative incidence of peptic ulcer from time of randomization, by random aspirin assignment, withP value from log-rank test.

Irregularities over time are due to intermittent collection of these events after the trial.

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Appendix Figure 8.

Cumulative incidence of colorectal polyps from time of randomization, by random aspirin assignment, withP value from log-rank test.

Irregularities over time are due to intermittent collection of these events after the trial.

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Figure 3.

Posttrial incidence of colorectal cancer by randomized aspirin and posttrial aspirin use, unweighted(top) and weighted (bottom) by inverse propensity of posttrial aspirin use.

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Summary for Patients

The Effect of Low-Dose Aspirin on Colorectal Cancer Risk in Women

The full report is titled “Alternate-Day, Low-Dose Aspirin and Cancer Risk: Long-Term Observational Follow-up of a Randomized Trial.” It is in the 16 July 2013 issue of Annals of Internal Medicine (volume 159, pages 77-85). The authors are N.R. Cook, I.M. Lee, S.M. Zhang, M.V. Moorthy, and J.E. Buring.

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