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Carcinogenesis Advance Access published online on August 31, 2006
Carcinogenesis, doi:10.1093/carcin/bgl153
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received May 8, 2006
Revised July 24, 2006
Accepted August 18, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Association of p73 G4C14-to-A4T14 (GC/AT) polymorphism with breast cancer survival

Hongxia Li 1, Lihua Yao 1, Tao Ouyang 1, Jinfeng Li 1, Tianfeng Wang 1, Zhaoqing Fan 1, Tie Fan 1, Bin Dong 2, Benyao Lin 1, Jiyou Li 2, and Yuntao Xie 1 *

1 Breast Center, Beijing Cancer Hospital, Peking University School of Oncology, 100036, Beijing, P. R. China
2 Department of Pathology, Beijing Cancer Hospital, Peking University School of Oncology, 100036, Beijing, P. R. China

* To whom correspondence should be addressed.
Yuntao Xie, E-mail: zlxyt2{at}bjmu.edu.cn


  Abstract

p73 gene shares structural and functional similarities to p53, and plays an important role in modulating cell-cycle arrest and apoptosis. A common non-coding polymorphism of exon 2 of the p73 gene (designated as GC/AT) may affect gene expression, thus, it may lead to functional significance. The correlation of this polymorphism with breast cancer survival has not been investigated. In this study, by using genomic DNA p73 GC/AT polymorphism was detected by PCR-SSCP in 526 breast cancer patients with a median follow-up of 7.3 years. Among the 526 breast cancer patients, 4% of the patients were homozygous for the AT/AT genotype, 39% were heterozygous GC/AT, and 57% were homozygous for the GC/GC genotype. We found that patients with the GC/GC genotype had a significantly worse clinical outcome than did patients with the AT Variants (AT/AT or GC/AT genotype) (5-year disease-free survival, 74.2% vs 95.0% or 84.1%, P=0.02; 5-year overall survival, 78.9% vs 95.0% or 87.5%, P=0.01, respectively). As compared with the GC/AT and AT/AT genotypes, the GC/GC genotype remained an independent prognostic indicator of disease-free survival (HR 1.82, P=0.003) and overall survival (HR 1.99, P=0.004) in multivariate analysis. Our results suggest that the GC/GC genotype is significantly associated with poor prognosis in breast cancer and raise the possibility that analysis of p73 polymorphism may provide useful prognostic information for breast cancer patients. Additional independent studies are needed to confirm these findings.

Keywords: p73 polymorphism; breast cancer; prognosis.
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