More Aspirin for Less Cancer?
Authors: M. E. Martinez, E. R. Greenberg
Journal: JNCI Journal of the National Cancer Institute (2007)

More than a century after aspirin was first synthesized, its benefits continue to be discovered and now include everything from relief of headaches to cardiovascular disease prevention. Evidence pointing to an association between aspirin and reduced cancer risk is largely derived from epidemiologic studies, although laboratory experiments and a few clinical trials have provided support for this idea. The apparent anticancer effect of aspirin has been seen most consistently for gastrointestinal tract cancers and especially for colorectal cancer ( 1 ); it is thought to occur through the drug’s ability to inhibit cyclooxygenase enzymes, which are produced by the body when there is inflammation, although alternate hypotheses have been suggested ( 2 ). Prior epidemiologic studies of aspirin and cancer prevention have often lacked detailed information on the dosage and duration of aspirin use, and this fact may account for some of the reported inconsistencies in their results. In this issue of the Journal, Jacobs et al. ( 3 ) report on long-term use of adult-strength aspirin and risk of cancer using data from the American Cancer Society’s Cancer Prevention Study II (CPS II) Nutrition Cohort. The investigators collected information on aspirin use at the beginning of the study in 1982, with more detailed information collected between 1992 and 2001. They found a modest 15% relative reduction in risk of developing any cancer associated with daily use of adult-strength aspirin for 5 years or longer. The strongest inverse association was shown for colorectal cancer, but a weaker, although statistically signifi cant, inverse association for prostate cancer was also observed. Breast cancer occurrence also seemed to be decreased, but this result was not statistically signifi cant. There was no clear evidence of reduced risk for cancer associated with use of lower dose aspirin or for use that was less than daily or of less than 5-year duration. The detailed information on aspirin use in the CPS II from Jacobs et al. ( 3 ) permits a sharper view of the possible role of aspirin dose and duration in cancer prevention, and the results strongly point to an association that is confi ned to individuals who use adult-strength aspirin (360 mg) at least daily for 5 or more years. However, only about 2% of men and 1% of women who were surveyed in 1992 fell into this category , and they appear to include a group that differs from other study participants in important ways besides aspirin usage. The investigators report that this group was, on average, older and had more chronic medical conditions than the overall cohort ; thus, they were likely to be under closer medical surveillance. The investigators adjusted in their statistical analyses for a number of potential confounding variables and for measures of cancer screening behavior, but this process may not have fully accounted for confounding or for possible biases in cancer ascertainment . Nevertheless, it is unclear whether unrecognized confounding and bias in this study would magnify or diminish the associations found in the analyses. Two randomized controlled trials of aspirin and cardiovascular disease in men ( 4 ) and in women ( 5 ) tested low-dose aspirin against placebo; the duration of aspirin treatment in the men was 5 years, whereas in women, the intervention lasted 10 years. Both trials showed no reduction in cancer occurrence, fi ndings that are consistent with those from the report by Jacobs et al. ( 3 ). The results of clinical trials have not been entirely consistent, however, and one trial of colorectal adenoma prevention reported a reduction in