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Genetic variants of the p53 and p73 genes jointly increase risk of second primary malignancies in patients after index squamous cell carcinoma of the head and neck
Author(s) -
Zhang Yang,
Sturgis Erich M.,
Huang Zhigang,
Zafereo Mark E.,
Wei Qingyi,
Li Guojun
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26222
Subject(s) - genotype , medicine , oncology , hazard ratio , head and neck squamous cell carcinoma , proportional hazards model , head and neck cancer , cohort , head and neck , basal cell , gene , cancer , cancer research , genetics , surgery , biology , confidence interval
BACKGROUND: Because of the structural and biochemical similarities between the antitumor p53 and p73 proteins, the authors hypothesized that individuals who carry high‐risk genotypes of p53 codon 72 and p73 G4C14‐to‐A4T14 polymorphisms have a higher risk of developing second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). METHODS: A cohort of 1269 patients with index cases of SCCHN was recruited between May 1995 and January 2007 at The University of Texas MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for p53 codon 72 and p73 G4C14‐to‐A4T14 polymorphisms. A log‐rank test and Cox proportional hazard models were used to compare SPM‐free survival and SPM risk among different risk groups with the combined risk genotypes of the 2 polymorphisms. RESULTS: The data demonstrated that patients with p53 WP + PP and p73 GC/GC genotypes had a worse SPM‐free survival and an increased SPM risk compared with the corresponding p53 WW and p73 GC/AT + AT/AT genotypes. After combining the 2 polymorphisms, a borderline significantly or significantly reduced SPM‐free survival and increased SPM risk were observed in the medium‐risk group ( p53 WW and p73 GC/GC or p53 P carriers and p73 AT carriers) and high‐risk group ( p53 P carriers and p73 GC/GC) compared with low‐risk group ( p53 WW and p73 AT carriers), respectively. CONCLUSIONS: The results suggest an increased risk of SPM after index SCCHN with both p53 and p73 polymorphisms individually and in combination. Cancer 2011;. © 2011 American Cancer Society.