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.
The authors declare that they have no competing interests.
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.
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).
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.
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).
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’ original file for figure 112943_2012_999_MOESM1_ESM.pdf
Do KA, Johnson MM, Lee JJ, Wu XF, Dong Q, Hong WK, Khuri FR, Spitz MR: Longitudinal study of smoking patterns in relation to the development of smoking-related secondary primary tumors in patients with upper aerodigestive tract malignancies. Cancer. 2004, 101: 2837-2842. 10.1002/cncr.20714 CrossRefPubMed
Minard CG, Spitz MR, Wu X, Hong WK, Etzel CJ: Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer. Cancer. 2006, 106: 2636-2644. 10.1002/cncr.21928 CrossRefPubMed
He G, Kuang J, Huang Z, Koomen J, Kobayashi R, Khokhar AR, Siddik ZH: Upregulation of p27 and its inhibition of CDK2/cyclin E activity following DNA damage by a novel platinum agent are dependent on the expression of p21. Br J Cancer. 2006, 95: 1514-1524. 10.1038/sj.bjc.6603448 PubMedCentralCrossRefPubMed
Kibel AS, Suarez BK, Belani J, Oh J, Webster R, Brophy-Ebbers M, Guo C, Catalona WJ, Picus J, Goodfellow PJ: CDKN1A and CDKN1B polymorphisms and risk of advanced prostate carcinoma. Cancer Res. 2003, 63: 2033-2036. PubMed
Choi HR, Tucker SA, Huang Z, Gillenwater AM, Luna MA, Batsakis JG, El-Naggar AK: Differential expressions of cyclin-dependent kinase inhibitors (p27 and p21) and their relation to p53 and Ki-67 in oral squamous tumorigenesis. Int J Oncol. 2003, 22: 409-414. PubMed
Kawamata N, Morosetti R, Miller CW, Park D, Spirin KS, Nakamaki T, Takeuchi S, Hatta Y, Simpson J, Wilcyznski S: Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in human malignancies. Cancer Res. 1995, 55: 2266-2269. PubMed
Moffatt KA, Johannes WU, Hedlund TE, Miller GJ: Growth inhibitory effects of 1alpha, 25-dihydroxyvitamin D(3) are mediated by increased levels of p21 in the prostatic carcinoma cell line ALVA-31. Cancer Res. 2001, 61: 7122-7129. PubMed
Pruneri G, Pignataro L, Carboni N, Buffa R, Di Finizio D, Cesana BM, Neri A: Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer. J Clin Oncol. 1999, 17: 3150-3159. PubMed
Gayther SA, Song H, Ramus SJ, Kjaer SK, Whittemore AS, Quaye L, Tyrer J, Shadforth D, Hogdall E, Hogdall C: Tagging single nucleotide polymorphisms in cell cycle control genes and susceptibility to invasive epithelial ovarian cancer. Cancer Res. 2007, 67: 3027-3035. 10.1158/0008-5472.CAN-06-3261 CrossRefPubMed
Chedid M, Michieli P, Lengel C, Huppi K, Givol D: A single nucleotide substitution at codon 31 (Ser/Arg) defines a polymorphism in a highly conserved region of the p53-inducible gene WAF1/CIP1. Oncogene. 1994, 9: 3021-3024. PubMed
Warren S, Gates O: Multiple primary malignant tumors: a survey of the literature and statistical study. Am J Cancer. 1932, 51: 1358-
- 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
Erich M Sturgis
- BioMed Central
Neu im Fachgebiet Onkologie
e.Med Kampagnen-Visual, Mail Icon II