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

Authors

  • Yang Zhang MD,

    1. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
    2. Department of Otolaryngology and Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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  • Erich M. Sturgis MD, MPH,

    1. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
    2. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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  • Zhigang Huang MD,

    1. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
    2. Department of Otolaryngology and Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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    • We thank Ms. Margaret Lung, Ms. Angeli Fairley, Ms. Liliana Mugartegui, and Ms. Kathryn Tipton for assistance with patient recruitment, and Dr. Chong Zhao and Ms. Yingdong Li for laboratory assistance.

  • Mark E. Zafereo MD,

    1. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
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  • Qingyi Wei MD, PhD,

    1. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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  • Guojun Li MD, PhD

    Corresponding author
    1. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
    2. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
    • Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030

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    • Fax: (713) 794-4662


  • The first and third authors contributed equally to this article.

Abstract

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.

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