This study suggests that p53 codon 72 polymorphisms play a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in a Chinese population.
Modulation of wild-type p53 activity by mutant p53R273H depends on the p53 responsive element (p53RE). A comparative study between the p53REs of the MDM2, WAFI/Cip1 and Bax genes in the lung cancer environment. WAFI/Cip1 = WAF1/Cip1.
Our results indicate that p53 mutations in exon 7 might be associated with increased radiation sensitivity in these human lung cancer cell lines, but our data should be interpreted with caution since several other explanations might exist regarding what determines the response towards radiation.
Using the April 2000 update of the p53 mutation database of the International Agency for Research on Cancer together with the primary literature, we confirm that the frequency of p53 G-->T transversions in lung cancer of smokers is about three times higher than their frequency in lung cancer of nonsmokers and in most other smoke-unrelated cancers.
Aim of our study was to evaluate the relationship between the polymorphisms of TP53 pathway genes <i>TP53</i>, <i>MDM2</i>, <i>MDM4</i>, the polymorphisms of HPV-associated genes <i>MTHFR</i>, <i>CASP8</i>, <i>CCR5</i>, and HPV infection with survival of LC patients.SNPs were genotyped using PCR-RFLP. qRT-PCR was used to detect, identify, and quantify HPV.
The identification of gene mutations in lung cancer has led to the development of inhibitory therapies, including antisense oligonucleotides and direct injection of tumor-suppressor genes, such as wild-type p53.
Multivariate regression analysis showed a moderate but statistically significant risk of lung cancer overall and especially of squamous-cell carcinoma (OR, 1.65; CI, 1.10-2.47) for TP53 72Pro allele carriers.
Despite the fact that many of the genetic alterations, including loss of heterozygocity in the 3p chromosome locus and point mutations in the tumor-suppressor genes TP53 and retinoblastoma (RB1), occur in nearly all histopathologic types of lung cancer, the frequency and the "timing" of their occurrence seems to differ between small-cell lung cancer (SCLC) cells, that are characterized by neuroendocrine differentiation, and non-small-cell lung cancer (NSCLC) cells.
The high formation of BPDE-N(2)-dG adducts in bronchial epithelial cells and investigations showing that the profile of mutations induced by BPDE in these cells is similar to that seen in the p53 gene isolated from human lung tumors implicates benzo[a]pyrene as important carcinogen in tobacco-induced lung cancer in human beings.
Multiple logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the risk of p53 mutation associated with polymorphisms of hOGG1 and APE1 in lung cancer.
After adjusting gender and tumor type, the major contributors to p53 degradation in lung cancer patients were determined to be p53 codon72 polymorphism and HPV 16/18 E6 oncoprotein expression.
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.
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.
Activation to a large extent of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and mutations in the p53 gene are involved in lung cancer therapeutic resistance.
Because the p53 recessive oncogene is mutated and anti-p53 antibodies frequently occur in cancer patients, we wondered if the development of anti-HuD antibodies signaled the presence of HuD mutations in lung cancer.