The authors studied cultured skin fibroblasts of 64 patients with lung cancer for constitutive mutations of the p53 tumor suppressor gene by using polymerase chain reaction and single-strand conformation polymorphism covering the entire coding region. The patients were considered to be genetically predisposed because lung cancer had developed in 25 of them before age 46 and because 42 of them had at least one first-degree relative with lung cancer. One mutation was detected at position 235 coding for serine instead of asparagine in the conserved DNA binding domain. The Pro/Pro genotype at codon 72 of p53, considered to harbor an increased risk for lung cancer, could not be detected with increased frequency in this study's patients. From these data, the authors conclude that constitutive variations of the p53 gene do not represent a major genetic determinant for lung cancer.