Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer
Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer
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DOI：
10.1200/jco.2005.02.9439
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发表时间：
2006-05-01
影响因子：
45.3
通讯作者：
Habuchi, T
中科院分区：
文献类型：
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作者：
Tsuchiya, N;Wang, L;Habuchi, T
目的转移性前列腺癌的预后在个体之间存在显著差异。虽然已经提出了各种临床和生化预后因素的生存，这些患者的进展和治疗反应也可以由宿主遗传因素定义。在这项研究中，我们评估了遗传多态性作为预后预测转移性prostate cancer.Patients和方法111例前列腺癌患者骨转移的诊断参加了这项研究。采用聚合酶链反应-限制性片段长度多态性技术或自动测序仪对13个多态性位点进行基因分型。长等位基因（超过18个[CA]重复）的胰岛素样生长因子-I（IGF-I）和长等位基因细胞色素P450（CYF）19的重复序列（超过7个[TTTA]重复序列）与更差的癌症特异性生存率显著相关（对数秩检验分别为P=.016和.025）。IGF-I或CYP 19多态性的长等位基因的存在是死亡的独立危险因素（分别为P= 0.019或0.026）。此外，IGF-I和CYP 19多态性的长等位基因的存在是生存的更强预测因素（P=.001）。结论转移性前列腺癌患者的预后受到内在遗传因素的影响。IGF-I（CA）重复和CYP 19（TTTA）重复多态性可能是前列腺癌患者诊断时骨转移的新预测因子。
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 (CYF) 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.