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Open Access Research

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

Zhongqiu Wang12, Erich M Sturgis13, Fenghua Zhang14, Dapeng Lei156, Zhensheng Liu3, Li Xu1, Xicheng Song17, Qingyi Wei3 and Guojun Li13*

Author Affiliations

1 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

2 Department of Radiology, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

3 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

4 Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051, China

5 Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan Shandong 250012, China

6 Key Laboratory of Otolaryngology, Ministry of Health, Jinan, Shandong 250012, China

7 Department of Otolaryngology-Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai 264000, China

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Molecular Cancer 2012, 11:17  doi:10.1186/1476-4598-11-17

Published: 26 March 2012

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.

Keywords:
p21; p27; Squamous cell carcinoma of head and neck; Second primary malignancy; Genetic susceptibility; Polymorphism