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p21 plays an important role in modulating cell cycle control, inducing apoptosis, and inhibiting cell growth, subsequently affecting cancer risk. We investigated the association between two putatively functional single-nucleotide polymorphisms (SNPs) ofp21(p21C98A andp21C70T) among 1282 patients diagnosed with incident squamous cell carcinoma of the head and neck (SCCHN) and risk of second primary malignancy (SPM) in an ongoing molecular epidemiology study. We used Log-rank test and Cox proportional hazard models to assess the association of these two SNPs with SPM-free survival and SPM risk. We found that patients with eitherp21variant genotypes of the two polymorphisms had a significantly reduced SPM-free survival compared with patients with eitherp21wild-type homozygous genotypes (Log-rank test,P = 0.0016). Compared with patients having thep2198 CC andp2170 CC genotypes, the patients havingp2198 CA/AA andp2170 CT/TT variant genotypes had a significantly greater risk of developing SPM, respectively, [hazard ratio (HR) = 1.80, 95% CI = 1.14–2.82 forp21C98A and HR = 1.82, 95% confidence interval (CI) = 1.16–2.85 forp21C70T]. Moreover, after combining the variant genotypes of two SNPs, patients with variant genotypes had a significantly moderately increased risk for SPM compared with patients with no variant genotypes (HR = 2.00, 95% CI = 1.26–3.00), and the risk was particularly pronounced in several subgroups. Our results support an increased risk of SPM after index SCCHN with bothp21polymorphisms individually and in combination.

carcinogenesis

Genetic polymorphisms of               p21               and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck