Distinct pattern of TP53 mutations in squamous cell carcinoma of the esophagus in Iran

Extremely high rates of squamous cell carcinoma of the esophagus (SCCE), ar e observed in Iran,, reflecting unknown, genetic and/or epidemiological ris k factors. Among genetic alterations, in SCCE,: TP53: mutations are the mos t frequent, vary among populations, and may provide clues on etiological me chanisms. We have analysed mutations in TP53 (exons 5-8): in 98 SCCE from I ran by temporal temperature get electrophoresis and direct sequencing. We f ound 58, mutations, in 49 patients, (50%,), with a high prevalence of C to T transitions at CpG dinucleotides (29.3%). The TP53 mutation pattern in Ir an was significantly different from that observed in SCCEs from high incide nce areas of China and Western Europe (P=0.007)., Moreover, the prevalence of mutations at A:T base pairs, (transitions and transversions) was higher in men than in women (38.7%, vs 11.1%, P=0.033). COX-2 overexpression was, detected in 69% of the cases evaluated (24/35), without significant associa tion with TP53, mutation. Accumulation of nitrotyrosine, a marker of protei n damage by excess, levels of nitric oxide, was observed in tumor cells, in six of 16 cases analysed. These results are consistent with the hypothesis that several factors are involved in TP53 mutagenesis, in Iran., These fac tors include a baseline of chronic inflammatory stress, which may have a mu ltiplicative impact on the sensitivity of esophageal cells to exogenous fac tors of risk.