Null Results in Brief Cyclooxygenase 2 Polymorphism (ValAla), Nonsteroidal Anti-inflammatory Drug Use and Breast Cancer in African American Women

Nonsteroidal anti-inflammatory drugs (NSAID) have been associated with reduced risks of colon cancer, breast cancer, and other cancer sites (1, 2). We previously reported a strong inverse relationship between NSAID use and breast cancer in a North Carolina study, with a suggestion of stronger associations among African Americans (3). One hypothesized mechanism for the reduction in cancer risk by NSAIDs is the inhibition of cyclooxygenase 2 (COX2), which is overexpressed in various cancer types and is thought to stimulate angiogenesis and inhibit apoptosis (1). A polymorphism in the COX2 gene [valine to alanine at residue 511 (ValAla)] has been identified in African Americans that results in a conformation change in the enzyme near its active site, and it has been hypothesized this polymorphism could modify biochemical function or change the response to NSAIDs (4, 5). In a recent paper, carriers of this polymorphism seemed to be at reduced risk for colon adenomas [odds ratio (OR), 0.56; 95% confidence interval (95% CI), 0.25-1.27] and colon cancer (OR, 0.67; 95% CI, 0.281.56; ref. 5). In this report, we describe the relationship between the COX2 ValAla polymorphism, NSAIDs, and breast cancer in a case-control study in North Carolina.