XPC, XPD/ERCC2, UMPS, CYP1b1 and XRCC5, single nucleotide polymorphisms (SNPs) in head and neck cancer

Abstract

5588 Background: SNPs located in the exonic region of XPC, XPD/ERCC2, UMPS, CYP1b1 and in the 3'UTR region of XRCC5 are involved in nucleotide excision repair and drug metabolism. We analyzed these SNPs and correlated the results with time to relapse (TTR), survival and response in head and neck cancer patients (p). Methods: PCR allelic discrimination (ABI Prism 7700 sequencer detector) was used to examine SNPs in DNA from tumor tissue obtained from 190 head and neck cancer p accrued from June 1985 to July 2002. Results: Characteristics of the initial 190 p: median age, 69 years; 170 PS 0–1, 20 PS >2; stage: I-39, II-24, III-32, IV-95. The most frequent tumor location was larynx (83p). Locoregional tumor progression was observed in 62% of p. 80% of p received concomitant chemoradiotherapy. Frequencies of genotypes: XPC: 82 TT, 105 TG; XPD/ERCC2: 70 AA, 89 AC, 31 CC; UMPS: 142 GG, 48 GC; CYP1b1: 50 CC, 106 CG, 34 GG; XCRR5: 146 AA, 39 AG. A correlation was found between XPD/ERCC2 and XRCC5 (P<0.04). No other correlation between genotypes was observed. TTR for all p was 16.5 months (m) (95%CI, 9.6–23). TTR was 15 m for UMPS GG vs 10 m for UMPS GC at pharynx (P=0.05), 26 m for CYP1b1 CC vs 50 m for CYP1b1 CG+GG at larynx (P=0.008), and 8.3 m for CYP1b1 CC vs 14.6 m for CYP1b1 CG+GG at pharynx (P=0.008). Overall median survival was 30.3 m but has not been reached for p with different genotypes. Response rate in p receiving concommitant chemoradiotherapy was 86% for p with UMPS CC vs 14% for p with UMPS CG (P=0.03), and 14% for p with CYP1b1 CC vs 86% for p with CYP1b1 CG+GG (P=0.04). Conclusions: CYP 1b1 and UMPS are expressed mainly in larynx and pharynx tumors and may be predictive markers in head and neck cancer. No significant financial relationships to disclose.