Both the nucleotide excision repair (NER) pathway and glutathione S-transferase (GSTP1) phase II metabolic enzymes have independently been implicated as important factors in modulating overall cancer survival and responsiveness to platinum based chemotherapy agents in a variety of tumor types. Here, we evaluated the role of genetic variation in both of these pathways on head and neck squamous cell carcinoma (HNSCC) survival, screening 381 cases. The mean age of HNSCC diagnosis among these patients was 59 years, the mean follow-up time was 26.5 months and a total of 81 deaths (50 with disease) were observed. Among these cases, 69 received platinum based therapy, either alone or in combination. Kaplan-Meier survival curves were generated to evaluate the impact of a panel of NER and GSTP1 polymorphisms’ effect on progression-free and overall survival. Hazard ratios (HR) by the Cox-proportional hazard regression were calculated after adjustment for age and gender. Among the ten polymorphisms screened, only the ERCC2 (XPD) Lys751Gln was significantly associated with improved survival times among platinum treated cases (HR=0.4, 95% CI 0.2-0.9, p<0.04). A similar trend towards significance for the GSTP1 1le105Val was also observed. Median survival time was 44 months (37.5-51.6) for the ERRC2 variant allele carriers vs. 34 (20.8-47.3) months for nonvariant carriers. In non-platinum treated patients, none of the screened genotypes were predictive of overall survival. No statistically significant interaction was detected between the XPD and GSTP1 genotypes. These findings suggest that genetic polymorphisms in the NER and GSTP1 genes may modulate overall HNSCC prognosis as well as response to platinum-based chemotherapy agents, independent of histology at diagnosis. Supported in part by NIH 1P50 CA097190.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA