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Annals of Oncology Advance Access originally published online on June 11, 2008
Annals of Oncology 2008 19(10):1734-1741; doi:10.1093/annonc/mdn368
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

gastrointestinal tumors

Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer

G. Lurje1, W. Zhang1, A. M. Schultheis1, D. Yang2, S. Groshen2, A. E. Hendifar1, H. Husain1, M. A. Gordon1, F. Nagashima1, H. M. Chang1 and H.-J. Lenz1,2,*

1 Division of Medical Oncology
2 Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, USA

* Correspondence to: Dr H.-J. Lenz, Division of Medical Oncology, University of Southern California, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. Tel: +1-323-865-3967; Fax: +1-323-865-0061; E-mail: lenz{at}usc.edu

Background: Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage III colon cancer who are more likely to benefit from adjuvant chemotherapy. The present study analyzed a subset of 10 polymorphisms within eight genes involved in the tumor angiogenesis pathway and their impact on prognosis in stage III colon cancer patients treated with adjuvant chemotherapy.

Patients and methods: Blood samples were obtained from 125 patients with locally advanced colon cancer at University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR–restriction fragment length polymorphism and 5'-end [{gamma}-33P] ATP-labeled PCR protocols.

Results: Polymorphisms in vascular endothelial growth factor (VEGF) (C+936T; P = 0.003, log-rank test) and interleukin-8 (IL-8) (T–251A; P = 0.04, log-rank test) were independently associated with risk of recurrence in stage III colon cancer patients. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of VEGF C+936T and IL-8 T–251A were associated with a higher likelihood of developing tumor recurrence (P < 0.001).

Conclusion: High expression variants of VEGF C+936T and IL-8 T–251A were associated with shorter time to tumor recurrence, indicating that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for tumor recurrence.

Key words: angiogenesis, colon cancer, tumor recurrence, VEGF

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007.

Received for publication December 8, 2007. Revision received April 7, 2008. Accepted for publication April 28, 2008.


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