Association of Long-term Use of Low-Dose Aspirin as Chemoprevention With Risk of Lung Cancer

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Lung cancer was the most commonly diagnosed cancer (1.8 million cases; 12.9% of all cancer cases) and the most common cause of cancer death (1.6 million deaths; 19.4% of all cancer deaths) in 2012 worldwide. The risk of lung cancer remains elevated after smoking cessation,and 15% of men and 53% of women with lung cancer are lifelong nonsmokers. Given this significant health burden, additional approaches for preventing lung cancer have been suggested, including regular aspirin use. Previous studies of aspirin use in patients with cardiovascular disease have suggested that low-dose aspirin use is beneficial in reducing the risk of cancer in a duration-dependent manner.

The antineoplastic effect of aspirin may be associated with the inhibition of cyclooxygenase-1 (COX-1)–mediated platelet activation. Inhibition of arterial thrombosis by aspirin impedes the development and progression of certain cancers.Cyclooxygenase-2 is known to be involved in the inflammatory process, and inhibition of COX-2–derived prostaglandin E2 formation by aspirin induces inhibition of cell proliferation and reduction of angiogenesis and immunomodulation through the production of lymphocytes in the peripheral blood. Cyclooxygenase-2 is expressed at high levels in human lung cancer tissue, especially in adenocarcinoma.

Although the use of low-dose aspirin for more than 5 years was associated with decreased risk of lung cancer, particularly among elderly participants and among people without diabetes, the observed effect size was quite modest. Future prospective studies are needed to determine whether there is a causal association.

According to the results of 2 meta-analyses, despite significant findings on aspirin use and lung cancer risk among case-control studies, the chemopreventive effects of aspirin on lung cancer risk in cohort studies were controversial. A pooled analysis of randomized trials with long-term follow-up showed that daily aspirin use reduced death due to lung cancer.Thus, the association between low-dose aspirin use and the risk reduction of lung cancer, the appropriate duration of aspirin use for chemoprevention, and the specific subgroups expected to benefit more from low-dose aspirin use are still inconclusive.