GERM-LINE POLYMORPHISMS OF P53 AND CYP1A1 GENES INVOLVED IN HUMAN LUNG-CANCER

The p53 tumor suppressor gene is mutated in diverse types of human can cer, and the normal allele encodes a nuclear protein that regulates ex pression of cell cycle-related genes as a transcription factor. The wi ld-type of p53 protein exists as at least two forms of variants among human populations, ascribed to amino acid replacement at codon 72 of A rg by Pro. In this study, we show that this germ line Arg-Pro polymorp hism at codon 72 of the p53 gene is associated with genetically determ ined susceptibility to smoking-induced lung cancer; a susceptible geno type Pro/Pro has a 1.7-fold higher risk of this cancer compared with o ther genotypes. This p53 polymorphism modulates risk to smoking-induce d lung cancer independently of other genetic risk factors such as germ line polymorphism of CYP1A1 or GST1 genes.