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p53 mutation and cancer

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Esophageal cancer

The incidence of esophageal cancer has risen in recent decades, coinciding with a shift in histologic type and primary tumor location. Adenocarcinoma of the esophagus is now more prevalent than squamous cell carcinoma in the United States and western Europe, with most tumors located in the distal esophagus. The cause for the rising incidence and demographic alterations is unknown. While risk factors for squamous cell carcinoma of the esophagus have been identified (tobacco, alcohol, diet, etc.), the risk factors associated with esophageal adenocarcinoma are less clear. The presence of Barrett's esophagus is associated with an increased risk of developing adenocarcinoma of the esophagus, and chronic reflux is considered the predominate cause of Barrett's metaplasia. The results of a population-based, case-controlled study from Sweden strongly suggest that symptomatic gastroesophageal reflux is a risk factor for esophageal adenocarcinoma. The frequency, severity, and duration of reflux symptoms were positively correlated with increased risk of esophageal adenocarcinoma. Fewer than 50% of esophageal cancers are squamous cell carcinomas. Adenocarcinomas, typically arising in Barrett's esophagus, account for at least 50% of malignant lesions, and the incidence of this histology appears to be rising. Barrett's esophagus contains glandular epithelium cephalad to the esophagogastric junction. Three different types of glandular epithelium can be seen: metaplastic columnar epithelium, metaplastic parietal cell glandular epithelium within the esophageal wall, or metaplastic intestinal epithelium with typical goblet cells. Dysplasia is particularly likely to develop in the intestinal type mucosa.

Fore more information click here: http://cancer.med.upenn.edu/pdq_html/1/engl/100089.html

Spectrum of p53 mutations in esophagal cancer

The frequency of p53 mutations is higher in esophageal ADC compared to SCC

The pattern of p53 mutations is diferent in the two types.






Meta-analysis of p53 loss of function in Esophageal cancer.
Points ; mean p53 activity as measured by transactivation with the WAF1promoter ; bars , 95 % CI. The mean and 95 % CI of p53 activity for all studies combined for a specific type of cancer is shown on the far left of each graph.
Horizontal line, mean of the combined studies. The publication code is indicated on the x-axis : the first number is an anonymous ID for the publication and the second number indicates the number of p53 mutants included in this study. Studies are presented from left to right in decreasing order of number of p53 mutants. The y-axis corresponds to p53 transactivation activity, with a value of 1.5 for the negative control and a value of 2.5 for 100 % of wild-type activity. Only studies with 5 or more p53 mutations are shown on the graph.

More information about this statistical analysis can be found in this article:

Soussi, T., Asselain, B., Hamroun, D., Kato, S., Ishioka, C., Claustres, M. and Beroud, C. (2006) Meta-analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection. Clin Cancer Res, 12, 62-69. Download the pdf



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