This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsuchiya, N. Articles by Habuchi, T. Search for Related Content PubMed PubMed Citation Articles by Tsuchiya, N. Articles by Habuchi, T. Related Articles Related Editorial

Impact of IGF-I and CYP19 Gene Polymorphisms on the Survival of Patients With Metastatic Prostate Cancer

Norihiko Tsuchiya, Lizhong Wang, Hiroyoshi Suzuki, Takehiko Segawa, Hisami Fukuda, Shintaro Narita, Masaki Shimbo, Toshiyuki Kamoto, Kenji Mitsumori, Tomohiko Ichikawa, Osamu Ogawa, Akira Nakamura, Tomonori Habuchi

From the Department of Urology and the Department of Medical Information Science Akita University School of Medicine, Akita; Department of Urology, Graduate School of Medicine, Chiba University, Chiba; and the Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Address reprint requests to: Tomonori Habuchi, MD, Department of Urology, Akita University School of Medicine, 1-1-1 Hondo Akita 010-8543, Japan; e-mail: thabuchi{at}doc.med.akita-u.ac.jp

PURPOSE: The prognosis of metastatic prostate cancer significantly differs among individuals. While various clinical and biochemical prognostic factors for survival have been suggested, the progression and response to treatment of those patients may also be defined by host genetic factors. In this study, we evaluated genetic polymorphisms as prognostic predictors of metastatic prostate cancer.

PATIENTS AND METHODS: One hundred eleven prostate cancer patients with bone metastasis at the diagnosis were enrolled in this study. Thirteen genetic polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism or an automated sequencer with a genotyping software.

RESULTS: Among the polymorphisms, the long allele (over 18 [CA] repeats) of insulin-like growth factor-I (IGF-I) and the long allele (over seven [TTTA] repeats) of cytochrome P450 (CYP) 19 were significantly associated with a worse cancer-specific survival (P = .016 and .025 by logrank test, respectively). The presence of the long allele of either the IGF-I or CYP19 polymorphisms was an independent risk factor for death (P = .019 or .026, respectively). Furthermore, the presence of the long allele of both the IGF-I and CYP19 polymorphisms was a stronger predictor for survival (P = .001).

CONCLUSION: The prognosis of metastatic prostate cancer patients is suggested to be influenced by intrinsic genetic factors. The IGF-I (CA) repeat and CYP19 (TTTA) repeat polymorphisms may be novel predictors in prostate cancer patients with bone metastasis at the diagnosis.

Supported by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan Grants No. 16591579, 00293861, 14207061, and 16591582, Princess Takamatsu Cancer Research Fund (2003), Public Trust Haraguchi Memorial Cancer Research Fund (2003), The Japanese Foundation for Prostate Research, and the grant-in-aid from the Japanese Urological Association (2003).

This study was presented at the Prostate Cancer: Epidemiology and Natural History (I) moderated poster session at the 100th Annual Meeting of the American Urological Association, San Antonio, TX, May 21-26, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Editorial

• Inherited Genetic Markers and Cancer Outcomes: Personalized Medicine in the Postgenome Era
  Timothy R. Rebbeck
  JCO 2006 24: 1972-1974 [Full Text]

This article has been cited by other articles:

				R. W. Ross, W. K. Oh, W. Xie, M. Pomerantz, M. Nakabayashi, O. Sartor, M.-E. Taplin, M. M. Regan, P. W. Kantoff, and M. Freedman Inherited Variation in the Androgen Pathway Is Associated With the Efficacy of Androgen-Deprivation Therapy in Men With Prostate Cancer J. Clin. Oncol., February 20, 2008; 26(6): 842 - 847. [Abstract] [Full Text] [PDF]

				P. D. Ryan and P. E. Goss The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer Oncologist, January 1, 2008; 13(1): 16 - 24. [Abstract] [Full Text] [PDF]

				O. Cussenot, A. R. Azzouzi, N. Nicolaiew, G. Fromont, P. Mangin, L. Cormier, G. Fournier, A. Valeri, S. Larre, F. Thibault, et al. Combination of Polymorphisms From Genes Related to Estrogen Metabolism and Risk of Prostate Cancers: The Hidden Face of Estrogens J. Clin. Oncol., August 20, 2007; 25(24): 3596 - 3602. [Abstract] [Full Text] [PDF]

				L. Lin, O. Ercan, J. Raza, C. P. Burren, S. M. Creighton, R. J. Auchus, M. T. Dattani, and J. C. Achermann Variable Phenotypes Associated with Aromatase (CYP19) Insufficiency in Humans J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 982 - 990. [Abstract] [Full Text] [PDF]

				T. R. Rebbeck Inherited Genetic Markers and Cancer Outcomes: Personalized Medicine in the Postgenome Era J. Clin. Oncol., May 1, 2006; 24(13): 1972 - 1974. [Full Text] [PDF]