TP53 alterations and patterns of carcinogen exposure in a U.S. population‐based study of bladder cancer

Abstract

The molecular pathology of bladder cancer has been the subject of considerable interest, and current efforts are targeted toward elucidating the interrelationships between individual somatic gene loss and both etiologic and prognostic factors. Mutation of the TP53 gene has been associated with more invasive bladder cancer, and evidence suggests that TP53 mutation, independent of stage, may be predictive of outcome in this disease. However, there is no consensus in the literature that bladder carcinogen exposure is associated with inactivation of the TP53 gene. Work to date has been primarily hospital based and, as such, subject to possible bias associated with selection of more advanced cases for study. We examined exposure relationships with both TP53 gene mutation and TP53 protein alterations in a population-based study of 330 bladder cancer cases in New Hampshire. Tobacco smoking was not associated with TP53 alterations. We found a higher prevalence of TP53 inactivation (i.e., mutation and nuclear accumulation) among hair dye users (odd ratio [OR] 5 4.1; 95% confidence interval [CI] 1.2-14.7), and the majority of these mutations were transversions. Men who had ''at risk'' occupations were more likely to have mutated TP53 tumors (OR 5 2.9; 95% CI 1.1-7.6). There also was a relative absence of TP53 mutation (OR 5 0.4; 95% CI 0.0-2.9) and TP53 protein alterations (OR 5 0.6; 95% CI 0.3-1.4) in bladder cancers from individuals with higher arsenic exposure. Our data suggest that there is exposure-specific heterogeneity in inactivation of the TP53 pathway in bladder cancers and that integration of the spectrum of pathway alterations in population-based approaches (capturing the full range of exposures to bladder carcinogens) may provide important insights into bladder tumorigenesis. ' 2005 Wiley-Liss, Inc.

Epigenetic Inactivation of SFRP Genes and TP53 Alteration Act Jointly as Markers of Invasive Bladder Cancer

“…There was no relationship between detection of promoter methylation and the percent of tumorous tissue in the sample (P < 0.8). This result is consistent with the previously reported finding (in the same samples) of no relationship between proportion of tumorous tissue and the measured presence of persistent TP53 protein by immunohistochemistry or TP53 mutation (16). To ensure that there was no bias in the amplification of substrate by tumor stage, we also did quantitative RT-PCR on a random subset of samples (10 invasive stage and 10 noninvasive stage) using the primers and probe for modified ACTB.…”

Association between DNA Repair Gene Polymorphisms and p53 Alterations in Japanese Patients with Muscle-Invasive Bladder Cancer

“…Several carcinogens, for ex- ample ultraviolet light, aflatoxin B 1 and cigarette smoke, have been found to cause mutations in the TP53 gene in some types of cancer, including bladder cancer [12][13][14] . Feasibly, some of the DNA damage related to such environmental agents is repaired by DNA repair enzymes.…”

“…These relatively common SNPs are thought to contribute to variations in DNA repair capacity [6][7][8][9] . The enzymes coded by these genes are considered to repair DNA damaged by some carcinogens causing mutations in the TP53 gene [12][13][14] . Thus, we selected these DNA repair genes as the focus of this study.…”

Intervention of nicotine on MNU-induced bladder cancer in rats

“…Therefore, in this experiment, the bladder cancer tissues in rat models treated with nicotine at different concentrations were detected for the expression of mt-p53 and the results showed that mt-p53 was positively expressed in the bladder cancer tissues and the expression was enhanced with the concentration of nicotine increasing. In the clinical studies related to p53 and bladder cancer, some scholars [11][12][13][14][15] confirmed that p53 gene mutations are closely related to the grade and stage of bladder cancer. If the tumor has p53 gene alteration, poor prognosis, shorter survival time and a higher mortality rate are usually shown.…”