Association of p53 codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck

BACKGROUND: p53 plays a critical role in cellular anticancer mechanisms, and has been correlated with second primary malignancy (SPM) development. A common polymorphism in codon 72 of p53 results in an amino acid substitution and could influence p53 function. The authors hypothesized that p53 codon 72 polymorphism may be associated with risk of SPMs and SPM-free survival among patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: A total of 1271 patients, who were diagnosed with incident SCCHN between May 1995 and January 2007, were genotyped and observed for SPM development. Log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk between the different genotype groups. RESULTS: The authors found significantly reduced SPM-free survival for patients with variant proline (Pro) 72 allele compared with patients with arginine (Arg) 72 homozygous genotype (log-rank test, P=.005). Compared with SCCHN patients with the p53 72Arg/Arg genotype, there was a significantly greater risk of SPM associated with the p53 72Arg/Pro genotype (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.17-2.61) and combined p53 72Arg/Pro+Pro/Pro (HR, 1.58;95% CI, 1.07-2.34). Furthermore, stratification analyses showed that the risk of SPM associated with p53 variant genotypes (Arg/Pro+Pro/Pro) was more pronounced in several subgroups. CONCLUSIONS: p53 codon 72 polymorphism could be a risk marker for genetic susceptibility to SPM in patients with primary SCCHN.