Statement of the Problem: Morbidity and mortality from squamous cell carcinoma of the head and neck (SCCHN) remain a significant public health problem. Almost 50% of the 40,400 newly diagnosed cases this year in the United States will end in either death or disease recurrence. Identification of patients at the time of diagnosis likely to undergo disease recurrence could help in decreasing morbidity and mortality. Genetic variability in repairing DNA damage may be an important prognostic indicator since DNA repair plays an important role in maintaining genomic stability. Materials and Methods: A prospective university cohort of 190 men and women with newly diagnosed SCCHN were enrolled for study and genotyped for two polymorphisms of a gene involved in DNA repair: X-ray cross complementing group 1 (XRCC1). Two polymorphisms have been identified at XRCC1: at codon 194, an arginine to tryptophan change in exon 6, and at codon 399, an arginine to glutamine change in exon 10. DNA was collected from either buccal swabs or serum lymphocytes. Polymorphisms of XRCC1 codon 194 and 399 genotypes were examined utilizing multiplex polymerase chain reaction and restriction fragment length polymorphism methodologies. Clinical information was collected on vital status, TNM stage, lymph node involvement, grade, and treatment. Disease recurrence was classified by the treating surgeon. Method of Data Analysis: Cox proportional hazards models were estimated utilizing SAS software. Results: Follow up time for the cohort ranged from 37 days to 64 months with an estimated overall median survival time of 42 months. Of the 190 patients enrolled in the study, three were lost to follow up. During the follow up period, 44 patients (23%) were diagnosed with disease recurrence. Of all variables examined, age, marital status, stage, distant metastasis, tumor size, therapy, and the XRCC1 399 GLN allele were predictive of disease recurrence. After multivariate modeling, individuals with the 399 GLN allele were 2.4 times less likely to have disease recurrence after adjustment for age and treatment. Conclusion: DNA repair is an important process in the management of cellular genomic instability. Our data suggest that the 399 GLN allele of the DNA repair gene XRCC1 is a strong predictor of disease recurrence. Further studies are needed to elucidate the 399 GLN repair pathways. References Olshan A, Watson M, Weissler M, et al: XRCC1 polymorphisms and head and neck cancer. Cancer Lett 178:181, 2002 Cheng L, Sturgis E, Eicher S, et al: Expression of nucleotide excision repair genes and the risk for squamous cell carcinoma of the head and neck. Cancer 94:393, 2002 Yu Z, Chen J, Ford B, et al: Human DNA repair systems: An overview. Environ Mol Mutagenesis 33:3, 1999 Funding Source: NIH grant CA61188; NIEHS grant P30ES10126; Oral and Maxillofacial Surgery Foundation.