Full-Strength Aspirin Over Time Has Ambiguous Effect on Cancer Risk

ATLANTA, April 10 -- Five years or more of daily adult-strength aspirin is associated with modest protection against colorectal, prostate, and breast cancers, investigators here reported.

However, daily low-dose aspirin (81 mg) used for cardiovascular protection is not associated with any additional protection against cancer, in keeping with other studies, reported Eric J. Jacobs, Ph.D., of the American Cancer Society, and colleagues, in the April 18 issue of the Journal of the National Cancer Institute.

The five-year findings emerged from a huge observational survey. But the investigators cautioned that a decade or longer will be needed to determine whether the association they found matters. At the moment, they wrote, "our results do not have immediate clinical implications."

In an accompanying editorial, Mara Elena Martnez, M.P.H., Ph.D., of the University of Arizona in Tucson, and E. Robert Greenberg, M.D., of Dartmouth Medical College in Hanover, N.H., pointed out that chronic use of full-strength aspirin (325 mg) may also have GI and hematologic consequences that obviate any potential anticancer benefit that may emerge in a long-term trial.

"Although such a trial merits careful consideration, it might be difficult to conduct it among average-risk individuals, given the toxicity of aspirin at doses greater than 80 mg/day," they wrote. "Thus, the authors appear justified in concluding that their results do not have immediate clinical implications, but they clearly illustrate the potential future importance of aspirin and other anti-inflammatory interventions as cancer control strategies."

The society's researchers found that daily use of adult-strength aspirin for a minimum of five years was associated with a roughly 15% lower overall cancer occurrence rate compared with no aspirin use. Most of the difference was accounted for by an approximate 30% reduction in colorectal cancer, 20% drop in prostate cancer, and 15% decline in breast cancer, although the latter was not statistically significant.

Dr. Jacobs and colleagues evaluated the association between self-reported daily use of adult-strength aspirin and occurrence rate of overall cancers and 10 specific cancer types among 69,810 men and 76,303 women. The participants were part of the nutrition cohort of the Cancer Prevention Study II, a prospective cancer mortality studied started in 1982.

Of this group, 1,618 men and 977 women reported using 325 mg or more aspirin daily for five years or longer. The authors compared the cancer occurrence rate in the regular aspirin users with that of non-users, calculating rate ratios with multivariable Cox proportional hazards regression.

They found that during from 1992 through June 2003, 10,931 men and 7,196 women in the total cohort were diagnosed with cancer. Among men who were long-term aspirin users, the adjusted rate ratio for all cancers was 0.84 (95% confidence interval, 0.76 to 0.93) compared with non-users.

Among women, the rate ratio for overall cancer was 0.86 (95% CI, 0.73 to 1.03), but this difference was not statistically significant (P=0.10).

The overall cancer incidence standardized to the age distributions of me in the study with long-term daily aspirin use was 1,858/100,000 person-years, compared with 2,163/100,000 person years for no aspirin use. Among women, the age-standardized incidence was 1,083/100,000 person years among daily aspirin users, compared with 1,169/100,000 person years for non-users.

The strongest protective effective for full-strength aspirin use was against colorectal cancers, with long-term users (men and women combined) having a rate of 0.68 (95% CI, 0.52 to 0.90) compared with none users.

Men who used aspirin chronically also had less prostate cancer (rate ratio vs. non-users, 0.81, 95% CI, 0.70 to 0.94). Women who used aspirin long-term had a non-significantly lower risk for breast cancer (rate ratio 0.83, 95% CI, 0.63 to 1.10).

"We found no association between long-term daily aspirin use and risk of lung cancer or other individual cancers examined (bladder cancer, melanoma, leukemia, non-Hodgkin's lymphoma, pancreatic cancer, and kidney cancer)," the investigators wrote. "Our null results with respect to lung cancer differ from those of a recent meta-analysis that reported 'regular' aspirin use to be associated with a 27% reduction in risk. However, results of this meta-analysis were influenced by substantial reductions in risk observed in two hospital-based case-control studies, whereas results from prospective studies have been inconsistent."

The authors noted that the study was limited by the observational design and its inherent inability to rule out confounding by unmeasured factors associated with both cancer risk and aspirin used. In addition, the study was not sufficiently powered to determine whether there might be an anti-cancer benefit to long-term use of low-dose aspirin.

The editorialists also pointed out the inherent limitations of the study. "Only about 2% of men and 1% of women who were surveyed in 1992 fell into the high dose aspirin 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," they wrote.

"Cost benefit analyses have indicated that low-dose aspirin is worth prescribing to men with a moderate risk of cardiovascular disease (>1% per year), but the drug's benefits relative to cost or risk are less certain at lower levels of individual risk," Dr. Martinez and Dr. Greenberg noted in their editorial. "Furthermore, low-dose aspirin is less clearly indicated for women due to the more limited effect on cardiovascular disease and the imprecision of the data on benefits and risks in women. Prophylactic aspirin use at higher doses would be less favorable for both women and men because of increased toxicity."

They also noted that "ironically, the strongest support for an anticancer effect of aspirin relates to colorectal cancer, but a highly effective method of preventing this cancer already exists (i.e., screening colonoscopy)."