These results suggest that a 'slipped mispairing' mechanism occurring during DNA replication may generate p53 intragenic deletion in human esophageal cancer, leading to abolished p53 mRNA expression.
The TP53 gene deletion rate was shown to be correlated with the level of differentiation and lymph node metastasis in EC; it may therefore be an important molecular marker for evaluating the condition of EC in patients.
In a large prospective cohort, p53Arg72Pro Pro/Pro was associated with a 2-fold increased risk of death in all esophageal cancers, whereas MDM2 T309G G/G was associated with a 7-fold increased risk of death in squamous cell carcinoma.
Mutations in exons 5-8 of the p53 gene were investigated by PCR-SSCP analysis using 10(3) sorted nuclei obtained from each endoscopic biopsy specimen of 16 patients with esophageal cancer.
A mutation of the p53 tumour suppressor gene is commonly identified in oesophageal cancer and dysplasia. p53 mutations can be anticipated immunohistochemically.
To understand the mutation spectrum and possible causative factors of esophageal cancer in this area, surgically resected human primary esophageal carcinomas from Linxian county were analyzed for p53 gene mutations in exons 5, 6, 7, and 8.
Our study shows that p53 point mutations occur more frequently in patients with esophageal cancer from this region than in patients from other areas of the world where the disease is prevalent.
Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2(*)1/(*)2) and less-active alcohol dehydrogenase-1B (ADH1B(*)1/(*)1) increase the risk of esophageal cancer in East Asian drinkers, and esophageal cancer multiplicity is strongly associated with ALDH2(*)1/(*)2. p53 alterations are key molecular events in multifocal carcinogenesis in the esophagus.
The p53 codon 72 genotype distribution was identical to published studies of normal Caucasian population, suggesting no general influence of this polymorphism on esophageal cancer risk in Germany.
Modeling gene-environment interactions in oral cavity and esophageal cancers demonstrates a role for the p53R72P polymorphism in modulating susceptibility.
The most common alterations found in esophageal cancers include allelic losses at chromosomes 3p, 5q, 9p, 9q, 13q, 17p, 17q and 18q, as well as mutations of p53 (mostly missense), Rb (deletions), cyclin DI (amplifications) and c-myc (amplifications).
The results demonstrate differential distribution of HPV infection and p53 mutation in esophageal cancer from different geographic regions of India and this could be due to variation in diet, drinking, and tobacco habit, including ethnic, socio-cultural and genetic variation.