title: 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.
abstract: 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 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).
  
  
  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.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Wang
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zhang
authors.forename: Dapeng
authors.initials: D
authors.lastname: Lei
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Xicheng
authors.initials: X
authors.lastname: Song
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27