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, and Tomonori Habuchi A B S T R A C T 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. J Clin Oncol 24:1982-1989. © 2006 by American Society of Clinical Oncology INTRODUCTION Prostate cancer is becoming one of the most com- mon cancers in males in Japan. 1 The introduction of prostate-specific antigen (PSA) screening has in- creased the identification of early-stage prostate cancer, and the establishment of surgical and radia- tion techniques may improve the outcome in these patients. Meanwhile, the prognosis of metastatic prostate cancer patients remains poor, although ap- proximately 80% of untreated patients respond to androgen deprivation therapy. However, it has also been acknowledged that the prognosis of metastatic prostate cancer differs significantly among individ- uals. 2 The prediction of prognosis and stratifying patients by their risk of progression are important for personalized treatments and follow-up strate- gies. To date, various clinical and biochemical pa- rameters as well as tumor characteristics have been reported to predict the survival of patients with met- astatic prostate cancer. As clinical and biochemical factors, lower performance status, pain score, extent of disease on bone scan, pretreatment serum testos- terone, serum alkaline phosphatase (ALP) and acid phosphatase, PSA, and lower hemoglobin (HGB) were reportedly associated with treatment response or patient survival. 3-7 Pathologic and immunohisto- chemical analyses also demonstrated that nuclear texture, oligosaccharide sialyl Lewis (x), c-erbB-2 (Her2/neu), and tissue factor could be predictors of survival. 5,8,9 The factors indicating the characteristics of cancer and polymorphisms as host genetic factors possibly influence the prognosis of cancer. Recently, various genetic polymorphisms were reportedly as- sociated with a risk of prostate cancer although the From the Department of Urology and the Department of Medical Information Science Akita University School of Medicine, Akita; Department of Urol- ogy, Graduate School of Medicine, Chiba University, Chiba; and the Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Submitted June 3, 2005; accepted November 22, 2005. 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 con- flicts of interest and author contribu- tions are found at the end of this article. 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@doc.med.akita-u.ac.jp. © 2006 by American Society of Clinical Oncology 0732-183X/06/2413-1982/$20.00 DOI: 10.1200/JCO.2005.02.9439 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 24  NUMBER 13  MAY 1 2006 1982 Downloaded from ascopubs.org by 3.90.200.63 on June 14, 2022 from 003.090.200.063 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.