We investigated the risk of basal cell carcinoma (BCC) in relation to a number of single nucleotide polymorphisms in genes involved in the inflammatory response. A case-control study including 322 BCC cases and a similar number of controls was nested in a population-based prospective study of 57,053 individuals (aged 50-64 at inclusion) in Denmark. NSAID use was associated with a slightly decreased risk of BCC (IRR=0.85, 95% CI=0.66-1.10). We found that two polymorphisms in COX-2, COX-2 A-1195G and T8473C were associated with risk of BCC. Carriers of the variant allele of COX-2 A-1195G had lower risk of BCC than homozygous wild type carriers (IRR=0.54, 95% CI=0.47-0.89). Homozygous carriers of the variant allele of COX-2 T8473C were at 2.27-fold higher risk of BCC (95% CI = 1.31-3.92) than homozygous wild type allele carriers. The polymorphisms IL6 G-174C, IL8 T-251A, PPARy2 Pro(12)Ala, ILI beta T-31C, and IL10 C-592A were not associated with risk of BCC. We found no statistically significant interaction between polymorphisms and NSAID use in relation to risk of BCC. While it cannot be ruled out that the present findings are due to chance, the results indicate that high COX-2 expression may increase risk of BCC while NSAID use may be protective. (c) 2007 Elsevier B.V. All rights reserved.