© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 3, 198-205,
February 5, 2003
© 2003 Oxford University Press
ARTICLE |
Cyclin D1 Genotype, Response to Biochemoprevention, and Progression Rate to Upper Aerodigestive Tract Cancer
Affiliation of authors: J. G. Izzo, P. L. C. den Hollander, I. M. Babenko, W. N. Hittelman (Department of Experimental Therapeutics), V. A. Papadimitrakopoulou, J. Keck, D. M. Shin, W. K. Hong (Department of Thoracic/Head and Neck Medical Oncology), A. K. El-Naggar (Department of Pathology), D. D. Liu, J. Jack Lee (Department of Biostatistics), The University of Texas M. D. Anderson Cancer Center, Houston.
Correspondence to: Julie G. Izzo, M.D., Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Box 19, 1515 Holcombe Blvd., Houston, TX 77030 (e-mail: jizzo{at}mdanderson.org).
Background: Altered cyclin D1 expression in advanced preinvasive lesions of the upper aerodigestive tract (UADT) is associated with an increased risk of developing cancer and histologic progression during and after combination biochemopreventive therapy (13-cis-retinoic acid, 
-interferon, and -tocopherol). Both alleles of the adenine (A)/guanine (G) cyclin D1 polymorphism located at nucleotide 870 encode two alternatively spliced transcripts, but the A allele preferentially encodes a protein with an extended half-life. We investigated whether the cyclin D1 genotype at nucleotide 870 was associated with baseline levels of cyclin D1 protein, post-treatment modulation of cyclin D1 protein levels, histologic response to treatment, and the outcome for subjects with preinvasive UADT lesions after biochemopreventive therapy. Methods: UADT tissue biopsy samples were obtained before and 6 and 12 months after biochemopreventive treatment from 31 individuals with advanced preinvasive UADT lesions. Tissues were examined for cyclin D1 genotype (by DNA single-strand conformation polymorphism analysis), for cyclin D1 protein expression (by immunohistochemistry), and for cyclin D1 gene copy number (by fluorescence in situ hybridization). Associations of cyclin D1 genotype with histologic response to therapy and time to progression to a higher degree of dysplasia or invasive cancer were investigated. All statistical tests were two-sided. Results: The A allele was associated with increased baseline cyclin D1 expression in the parabasal epithelial layer (16 of 18 AA/AG subjects versus four of nine GG subjects; P = .02), decreased histologic response to biochemopreventive treatment (six of 21 AA/AG subjects versus four of 10 GG subjects; P = .70), decreased favorable modulation of cyclin D1 expression by the treatment (seven of 18 AA/AG subjects versus eight of nine GG subjects; P = .02), and shorter progression-free survival (P = .05). Conclusions: The cyclin D1 A allele was associated with a diminished modulation of normal physiologic and treatment-induced decreased expression of cyclin D1, a decreased likelihood of response to biochemopreventive intervention, and an increased rate of progression to cancer development, findings that require validation in a larger cohort.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Szabo Assessing Efficacy in Early-Phase Cancer Prevention Trials: The Case of Oral Premalignancy Cancer Prevention Research, October 1, 2008; 1(5): 312 - 315. [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Lippman and J. V. Heymach The Convergent Development of Molecular-Targeted Drugs for Cancer Treatment and Prevention Clin. Cancer Res., July 15, 2007; 13(14): 4035 - 4041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Izzo, T.-T. Wu, X. Wu, J. Ensor, R. Luthra, J. Pan, A. Correa, S. G. Swisher, C. K.S. Chao, W. N. Hittelman, et al. Cyclin D1 Guanine/Adenine 870 Polymorphism With Altered Protein Expression Is Associated With Genomic Instability and Aggressive Clinical Biology of Esophageal Adenocarcinoma J. Clin. Oncol., February 20, 2007; 25(6): 698 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sims-Mourtada, J. G. Izzo, S. Apisarnthanarax, T.-T. Wu, U. Malhotra, R. Luthra, Z. Liao, R. Komaki, A. van der Kogel, J. Ajani, et al. Hedgehog: an Attribute to Tumor Regrowth after Chemoradiotherapy and a Target to Improve Radiation Response. Clin. Cancer Res., November 1, 2006; 12(21): 6565 - 6572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Huang, M. R. Spitz, J. Gu, J.J. Lee, J. Lin, S. M.Lippman, and X. Wu Cyclin D1 gene polymorphism as a risk factor for oral premalignant lesions Carcinogenesis, October 1, 2006; 27(10): 2034 - 2037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Kelloff, S. M. Lippman, A. J. Dannenberg, C. C. Sigman, H. L. Pearce, B. J. Reid, E. Szabo, V. C. Jordan, M. R. Spitz, G. B. Mills, et al. Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward Clin. Cancer Res., June 15, 2006; 12(12): 3661 - 3697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Lippman and J. J. Lee Reducing the "Risk" of Chemoprevention: Defining and Targeting High Risk--2005 AACR Cancer Research and Prevention Foundation Award Lecture. Cancer Res., March 15, 2006; 66(6): 2893 - 2903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Izzo, U. Malhotra, T.-T. Wu, J. Ensor, R. Luthra, J. H. Lee, S. G. Swisher, Z. Liao, K.S. C. Chao, W. N. Hittelman, et al. Association of Activated Transcription Factor Nuclear Factor {kappa}B With Chemoradiation Resistance and Poor Outcome in Esophageal Carcinoma J. Clin. Oncol., February 10, 2006; 24(5): 748 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ma, Q. Feng, D. Sekula, J. A. Diehl, S. J. Freemantle, and E. Dmitrovsky Retinoid Targeting of Different D-Type Cyclins through Distinct Chemopreventive Mechanisms Cancer Res., July 15, 2005; 65(14): 6476 - 6483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Hirsch and S. M. Lippman Advances in the Biology of Lung Cancer Chemoprevention J. Clin. Oncol., May 10, 2005; 23(14): 3186 - 3197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Lippman, J. Sudbo, and W. K. Hong Oral Cancer Prevention and the Evolution of Molecular-Targeted Drug Development J. Clin. Oncol., January 10, 2005; 23(2): 346 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. O. Shu, D. B. Moore, Q. Cai, J. Cheng, W. Wen, L. Pierce, H. Cai, Y.-T. Gao, and W. Zheng Association of Cyclin D1 Genotype with Breast Cancer Risk and Survival Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 91 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Schwartz, J. Rajendran, B. Yueh, M. D. Coltrera, M. LeBlanc, J. Eary, and K. Krohn FDG-PET Prediction of Head and Neck Squamous Cell Cancer Outcomes Arch Otolaryngol Head Neck Surg, December 1, 2004; 130(12): 1361 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Le Marchand, A. Seifried, A. Lum-Jones, T. Donlon, and L. R. Wilkens Association of the Cyclin D1 A870G Polymorphism With Advanced Colorectal Cancer JAMA, December 3, 2003; 290(21): 2843 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Yamazaki, K Hanami, T Nagao, A Asoh, I Sugano, and Y Ishida Increased cyclin D1 expression in cancer of the ampulla of Vater: relevance to nuclear {beta} catenin accumulation and k-ras gene mutation Mol. Pathol., December 1, 2003; 56(6): 336 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Sabichi, M.-F. Demierre, E. T. Hawk, C. E. Lerman, and S. M. Lippman Frontiers in Cancer Prevention Research Cancer Res., September 15, 2003; 63(18): 5649 - 5655. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Kurie Cyclin D1 Expression in the Field of Exposure: Another Piece in the Molecular Auerbach Puzzle J. Clin. Oncol., June 1, 2003; 21(11): 2056 - 2058. [Full Text] [PDF]
|
|