The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in LC were 37.0%, 46.2%, and 16.7%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively (p<0.01).
Thus, mutant p53 genes have been found in urine from patients with bladder cancer, mutant ras genes in stools from patients with colorectal and pancreatic cancers, and both mutant p53 and ras genes in sputum from patients with lung cancer.
The results of this study suggest that the p53 MspI polymorphism may modify the susceptibility to lung cancer as a single factor rather than in combination with BstUI polymorphism.
In two cases, the lung tumors exhibited a p53 mutation not present in the previously removed primary tumor and were therefore classified as new primary lung cancers.
When generally comparing TP53 mutation group with TP53 wild-type group, we confirmed the prognostic value of poor OS of TP53 in EGFR mutant lung cancers (HR 1.73, 95% CI 1.22-2.44, P = 0.002).
We show that lung epithelial expression of R270H and R172H (R273H and R175H in humans), common TRP53 mutants in lung cancer, combined with RB1 loss selectively results in two subtypes of neuroendocrine carcinoma, SCLC and large cell neuroendocrine carcinoma (LCNEC).
For example, characteristic p53 mutation spectra have been associated with: dietary aflatoxin B1 exposure and hepatocellular carcinoma; sunlight exposure and skin carcinoma; and cigarette smoking and lung cancer.
Significantly, codons 244 and 248 are mutational "hotspots" in nonsmall cell and small cell lung cancers, supporting a possible role of oxidation in p53 mutations leading to lung cancer.
We used genetic alterations in p53 gene as a discrimination marker of double primary lung cancers from single lung cancer with intrapulmonary metastasis.
Therefore, although smoking-related lung cancer unequivocally arises due to the mutagenic environment induced by tobacco carcinogens, this perspective provides a rationale for the preferential selection of lung-enriched V157, R158, and A159 mutant p53.
We selected eight genes, ATM serine/threonine kinase gene (ATM), BRCA2, DNA repair associated gene (BRCA2), checkpoint kinase 2 gene (CHEK2), EGFR, parkin RBR E3 ubiquitin protein ligase gene (PARK2), telomerase reverse transcriptase gene (TERT), tumor protein p53 gene (TP53), and Yes associated protein 1 gene (YAP1), on the basis of prior anecdotal association with lung cancer or genome-wide association studies.
Despite employing a comprehensive set of statistical tests including those sensitive to the detection of differences in early survival our data provide little evidence to support the tenet that the p53Arg72Pro polymorphism is a clinically useful prognostic marker for lung cancer.
Mutation of the p53 gene is the most frequently identified genetic change in human lung cancer; these findings suggest that simple immunohistological methods can provide strong evidence of such mutation.
Although no significant association between any single genetic variant and lung cancer risk was observed, when genetic variants were analyzed in combination, a significant effect on lung cancer risk was found for the variant allele in a combination of five genes involved in oxidative stress and inflammatory response: GSTM1 (null), MPO (-463A), OGG1 (326Cys), TP53 (72Pro) (alias p53), MMP1 (2G).
Furthermore, there was a dose-response relationship between the quantity of cigarettes consumed and the frequency of p53 mutations in lung cancer patients (P < 0.001).
We conducted p53 mutational spectrum analysis in second lung cancers after radiation therapy for Hodgkin's disease in the Netherlands and in Ontario, Canada.
These results indicate that (a) the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis; (b) a combination of four genetic alterations, including human telomerase reverse transcriptase overexpression, bypass of p16/RB and p53 pathways, and mutant K-RAS(V12) or mutant EGFR, is still not sufficient for HBECs to completely transform to cancer; and (c) EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention.