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Background Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN). Methods 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. Results 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 p27 109 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 (P trend = 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). Conclusions 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.

Background Several long noncoding RNAs (lncRNAs) are involved in oncogenesis. Methods and Results Our microarray analysis showed that numerous lncRNAs are dysregulated in hypopharyngeal squamous cell carcinoma (HSCC) tumor tissues as compared with normal tissues. Among those lncRNAs, urothelial carcinoma-associated 1 (UCA1) has been found to have an oncogenic role in HSCC. We confirmed the upregulation of UCA1 in HSCC by assessing its expression levels in a cohort of 53 patient tumors and paired non-tumor samples. In addition, we found that high UCA1 expression was significantly associated with advanced T category, late clinical stage, greater lymphatic invasion, and worse prognosis. Furthermore, in vitro experiments demonstrated that UCA1 functioned as an oncogene by promoting the proliferation and invasion and preventing the apoptosis of HSCC cells. Conclusions Taken together, our findings for the first time identify the role of UCA1 as a tumor promoter and a pro-metastatic factor in HSCC, demonstrating that UCA1 is a potential prognostic biomarker and therapeutic target in HSCC.