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The p53 tumor suppressor protein plays a critical role in the control of cell growth and apoptosis. A number of anti-cancer agents, including cisplatin, exert their biological effects via p53-dependent apoptosis. p53 gene mutations are the most common cancer-related genetic changes, found in more than 50% of human cancers. p53 mutations can cause the expression of abnormal proteins or result in complete loss of p53 expression. The p53 polymorphism in codon 72 of exon 4 results in a change from arginine (CGC) to proline (CCC). These two, p53Arg72 and p53Pro72, proteins do not differ in their ability to bind to DNA in a sequence-specific manner but do have distinct biochemical and functional properties, including their ability of signal apoptosis, susceptibility to HPV mediated E6 degradation, and response to chemotherapy in other tumor types. In the present study, we looked at p53 codon 72 polymorphism from 65 laryngeal tumor patients enrolled in the VA Laryngeal Cancer Group Study. The objective of this study is to determine if polymorphism in p53 influences response to chemotherapy or survival in advanced larynx cancer patients. DNA from paraffin embedded tissue samples was extracted using Qiagen kits. Genetic analysis of these samples was performed using polymerase chain reaction followed by direct sequencing of exon 4 of p53. p53 72Arg/Arg allele was most prevalent (63%) in these tumor samples followed by 72Pro/Pro (20%) and 72Arg/Pro (16.9%). Patients with Arg/Pro allele were most responsive to chemotherapy (100%, 7-0, complete or partial responders to non-responders) followed by patients with Arg/Arg allele (82%, 14-3). In contrast, patients with Pro/Pro were the least responsive to chemotherapy (62%, 5-3). Similarly, patients with Arg/Pro allele showed the best survival rate followed by patients with Arg/Arg allele. Patients with Pro/Pro allele showed the poorest survival rate. Taken together, our results suggest that Arg72 polymorphism is more prevalent in patients with squamous cell carcinoma of the larynx from the Department of Veterans Affairs larynx clinical trial and p53 72Arg/Pro polymorphism was best correlated with chemotherapy response and higher survival rate. This research is supported in part by NIH NCI grant (1 R01 CA83087) and University of Michigan’s Cancer Center Support Grant (5 P30 CA46592).

[Proc Amer Assoc Cancer Res, Volume 46, 2005]