The associations of p53 overexpression with p53 codon 72 genetic polymorphism and environmental toxin exposure in esophageal cancer.

J-M Lee MD PhD^a, M-T Wu MD ScD^b, Y-C Lee MD PhD^a, H-H Hsu MD^a, J-S Chen MD^a, T-Y Liu PhD^c

^aDepartment of Surgery, National Taiwan University Hospital, National Taiwan, , ^bGraduate Institute of Occupational Health and Safty, Kauhsiung Medical University, Kauhsiung Medical, , ^cDepartment of Medical Research and Education, Veteran General Hospital

Previously, we have found that the risk of esophageal cancer can be modified by the p53 codon 72 genetic polymorphism, or habits of consuming, tobacco, alcohol and areca quid. AIM: In this study, we investigated whether these environmental and genetic risk factors can further modulate the status of p53 overexpression in tumors of the esophageal cancer. METHODS: Using the technique of immunohistochemical staining we examined the status of p53 overexpression in 124 patients of esophageal cancer. The genotype of p53 codon 72 genetic polymorphiam was determined by PCR-RFLP. Their environmental exposure backgrounds were evaluated by structured questionnaires. RESULTS: We found that the presence of p53 over-expression was significantly associated with the history of cigarette smoke, alcohol drinking and areca chewing (p< 0.05). The risks of p53 over-expression was further enhanced with the accumulation of these factors, with ORs (95% CI) of 0.9 (0.16-5.05), 5.77 (1.47-22.87) and 6.40 (1.49-27.49) for the individuals exposed to one, two, or three of these factors respectively, which were adjusted with tumor T, and N staging, and history of neoadjuvant therapies. The status of p53 overexpression was also significantly affected by the p53 codon 72 genetic polymorphism. The p53 overexpression was more frequently found in the individuals with the p52 codon 72 Arg allele (p<0.05). Our data suggested that the p53 overexpression was associated with various environmental toxin exposures and the genetic polymorphism of p53 itself, which attributed to significant propensity to esophageal carcinogenesis.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 996 (Genetic & environmental interactions).