RALEIGH, N.C. – Postmenopausal women who used aspirin regularly had a significantly reduced risk of developing melanoma during long-term prospective follow-up, according to a Women’s Health Initiative observational study analysis.
The magnitude of this risk reduction grew with greater duration of aspirin use, reported Christina A. Gamba, a medical student at Stanford (Calif.) University.
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Women in this study who had been using aspirin regularly for 1-4 years at enrollment went on to have a 20% reduction in risk of developing incident melanoma.
During 12 years of prospective follow-up, women who at the time of study enrollment reported they had been taking aspirin regularly for less than a year had roughly an 11% reduction in the likelihood of developing incident melanoma, compared with aspirin nonusers. Those who had been using aspirin regularly for 1-4 years at enrollment went on to have a 20% risk reduction. And women on aspirin for 5 years or longer at enrollment were 30% less likely to develop melanoma than nonusers.
These relative risk figures were fully adjusted for age, education, income, skin type, melanoma risk factors, physical activity, vitamin D intake, smoking status, body mass index, sunburn history, time spent outdoors, sunscreen use, and medical indications for aspirin use, such as cardiovascular disease, she noted.
The findings suggest a possible chemopreventive effect for aspirin against the development of melanoma. As such, these data are consistent with other studies that have linked NSAIDs with decreased risks of breast, colorectal, and gastric cancer. The specific mechanism of benefit is thought to involve inhibition of cyclo-oxygenase-2, which is proinflammatory.
Ms. Gamba explained that her Women’s Health Initiative observational study analysis included 59,806 postmenopausal white women for whom complete pertinent data were available. During nearly 12 years of follow-up, 548 incident melanomas occurred among the study population: 255 were invasive; the rest were in situ.
At enrollment, 25% of women reported using aspirin regularly; their melanoma incidence during follow-up was 0.76%. Fifteen percent of subjects used nonaspirin NSAIDs; their melanoma incidence was 0.97%, which was identical to the rate in the 60% of women who were nonusers of any NSAIDs. Regular users of acetaminophen, a drug that relieves pain but doesn’t inhibit cyclo-oxygenase-2, had the same melanoma incidence as nonusers of aspirin and other NSAIDs.
Three-quarters of the aspirin users were on regular- or extrastrength formulations. There were too few women on low-dose aspirin to be able to draw any conclusions as to whether it, too, protected against melanoma, she said at the annual meeting of the Society of Investigative Dermatology.
The study included one measure of consistency: At 3 years of follow-up, 60% of women who reported taking aspirin regularly at baseline were still doing so, as were 35% of those who had been on nonaspirin NSAIDs at enrollment.
Audience members posed this question: If aspirin’s presumed chemoprevention mechanism involves the inhibition of cyclooxygenase-2, why didn’t users of nonaspirin NSAIDs enjoy a similar benefit? Ms. Gamba offered two possible theories. One is that users of nonaspirin NSAIDs took the medication less frequently, in contrast to aspirin users who generally took the drug on a daily basis.
The other possibility, she continued, is that aspirin curbs tumorigenesis through cyclo-oxygenase-independent mechanisms – perhaps by promoting apoptotic genes and/or inhibiting tumor-promoting genes.
All cases of melanoma in the Women’s Health Initiative were pathologically confirmed. Ms. Gamba and her investigators are now going back and examining the pathology reports to learn what specific types of melanoma were involved. They are also reanalyzing their aspirin/NSAID usage data, this time restricting the analysis to cases of in situ melanoma.
The Women’s Health Initiative Observational Study was sponsored by the National Institutes of Health. Ms. Gamba reported having no relevant financial conflicts.