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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Molecular Cancer 1/2012

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

Zeitschrift:
Molecular Cancer > Ausgabe 1/2012
Autoren:
Zhongqiu Wang, Erich M Sturgis, Fenghua Zhang, Dapeng Lei, Zhensheng Liu, Li Xu, Xicheng Song, Qingyi Wei, Guojun Li
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-4598-11-17) contains supplementary material, which is available to authorized users.
Zhongqiu Wang, Fenghua Zhang contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

ZW participated in the design of the study, data analysis, and manuscript writing. EMS participated in study design, statistical analysis and manuscript writing. FZ performed literature review and drafted the manuscript. DL participated in study design and helped to draft the manuscript. ZL carried out the laboratory analysis. LX participated in statistical analysis and helped to draft the manuscript. QW participated in study design, data analysis, and manuscript writing. GL participated in study design, data analysis and manuscript writing. All authors read and approved the final manuscript.

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 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 (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.
Zusatzmaterial
Authors’ original file for figure 1
12943_2012_999_MOESM1_ESM.pdf
Literatur
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