Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck

A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk.We found that patients with p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (Ptrend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6).These results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.In the United States, squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 50,000 new cancer cases, causing 11,480 deaths annually [1,2]. SCCHN has modest survival rates mainly because of second primary malignancies (SPM), comorbid illnesses, and index cancer recurrence [3]. A leading cause of mortality in such patients is the development of SPM [3]. Additional studies on host factors that predict SPM in SCCHN patients are needed so that intensive surveillance or targeted intervention for patients at high-risk of SPM may improve prognosis. In addition to smoking, alcohol drinking and cancer treatment as risk factors for SPM, genetic predisposition might also influence the development of SPM after index SCCHN [3-10].A common feature of human cancer is cell cycle deregulation, and cell cycle progression is governed by the activation cyclin and cyclin-dependent kinases (CDKs),