The existing epidemiologic literature was comprehensively reviewed to retrieve all epidemiologic studies (case control and cohort studies) that examined exposure to traditional over the counter nonsteroidal anti-inflammatory
drugs (OTC NSAIDs) and the risk of
cancers of the colon, breast, prostate and lung from 1980 forward. These
malignancies account for more that half of all
cancer deaths in the United States and the United Kingdom. Estimates of effects (relative risks or odds ratios) and 95% confidence intervals were abstracted from these reports for meta-analysis. Regular intake of OTC
NSAIDs produced highly significant composite risk reductions of 43% for
colon cancer, 25% for
breast cancer, 28% for
lung cancer, and 27% for
prostate cancer. Furthermore, in a series of case control studies, daily use of a selective
COX-2 inhibitor, either
celecoxib or
rofecoxib, significantly reduced the risk for each of these
malignancies. The evidence is compelling that
anti-inflammatory agents with selective or non-selective activity against cycloooxygenase- 2 (COX-2) have strong potential for the
chemoprevention of
cancers of the colon, breast, prostate and lung. Results confirming that COX-2 blockade is effective for
cancer prevention have been tempered by observations that some selective
COX-2 inhibitors pose a risk to the cardiovascular system. Nevertheless, meta-analysis of independent estimates from 72 studies provides no evidence that the selective
COX-2 inhibitor,
celecoxib, influences the relative risk of
cardiovascular disease (composite relative risk = 0.98, 95% CI = 0.88-1.10). Molecular studies reveal that over-expression of COX-2 is a prominent feature of premalignant and
malignant neoplasms. Evidence is accumulating that
carcinogenesis often evolves as a progressive series of highly specific cellular and molecular changes in response to induction of constitutive over-expression of COX-2 and the
prostaglandin cascade in the "inflammogenesis of
cancer".