Comprehensive assessment of P21 polymorphisms and lung cancer risk

The purpose of this study is to comprehensively evaluate potential functional polymorphisms in the P21 gene in relation to the risk of lung cancer. We first determined the frequencies of P21 polymorphisms in 27 healthy Koreans, and then examined three polymorphisms (-2266G > A, S31R, and IVS2 + 16G > C), based on their frequencies and haplotype-tagging status, in a case-control study. Individuals with at least one -2266A allele were at a significantly decreased risk of lung cancer compared with those harboring the -2266 GG genotype [adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.53-0.95, P = 0.02). The haplotypes (ht2-4) carrying 31R or IVS2 + 16C alleles were associated with a significantly decreased risk of lung cancer compared with the haplotype 31S/IVS2 + 16G, which carried wild-type alleles at both loci (adjusted OR = 0.65, 95% CI = 0.50-0.83, P = 0.007)]. When the -2266A allele and ht2-4 were considered to be protective alleles, the risk of lung cancer decreased in a dose-dependent manner as the number of protective alleles increased (P = 0.0002). These results suggest that a combined analysis of these three P21 polymorphisms might better predict the risk of lung cancer than the analysis of a single polymorphism.