p53-binding protein 1 (P53BP1) and p53 interact in the p53-mediated transcriptional activation and checkpoint in response to DNA damage. Because suboptimal repair for tobacco-induced DNA damage is associated with risk of squamous cell carcinoma of the head and neck (SCCHN), we hypothesized that potentially functional variants in P53BP1 and p53 may contribute to SCCHN risk.We genotyped variants of T-885G, Glu353Asp, and Gln1136Lys in P53BP1 and Arg72Pro, p53PIN3, and p53MspI in p53 in a case-control study of 818 SCCHN patients and 821 cancer-free controls. None of these genetic variants was associated with SCCHN risk in the single-locus analysis. However, the combined P53BP1 genotypes were associated with significantly decreased SCCHN risk among carriers of p53Pro72Pro, p53PIN3MM and p53IN6MM in a dose-response manner (trend test: P = 0.024, 0.016 and 0.016, respectively). Furthermore, the P53BP1 GGC haplotype carriers had a significantly reduced risk of SCCHN if they also had p53 homozygous variant genotypes, than those carrying haplotype TCA (adjusted OR = 0.48 for p53Pro72pro, 0.17 for p53PIN3 MM, and 0.16 for p53PIN6 MM). Also, carriers of 1-2 copies of the P53BP1 GGC haplotype had significantly decreased SCCHN risk if they also had 2 copies of the p53 MMM haplotype (OR = 0.08, 95% CI 0.01-0.50). There was evidence of interaction between P53BP1and p53 diplotypes (P = 0.017). These data suggest that protective effects of P53BP1 variants on SCCHN risk are confined to p53 variant genotype/haplotype carriers. However, this finding needs to be verified in larger studies (Supported by National Institutes of Health Grant R01 ES11740, CA100264, and CA16672).

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