<p>Abstract</p> <p>Background</p> <p>Cell cycle deregulation is common in human cancer, and alterations of <it>p27 </it>and <it>p21</it>, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that <it>p27 </it>T109G polymorphism individually or in combination with <it>p21 </it>(C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN).</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>We found that patients with <it>p27 </it>109 TG/GG, <it>p21 </it>98 CA/AA and <it>p21 </it>70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding <it>p27</it>109 TT, <it>p21 </it>98 CC, and <it>p21 </it>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 (<it>P</it><sub>trend </sub>= 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).</p> <p>Conclusions</p> <p>These results suggest that <it>p27 </it>T109G polymorphism individually or in combination with <it>p21 </it>(C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.</p
