Wang Lizhong, Habuchi Tomonori, Tsuchiya Norihiko, Mitsumori Kenji, Ohyama Chikara, Sato Kazunari, Kinoshita Hidehumi, Kamoto Toshiyuki, Nakamura Akira, Ogawa Osamu, Kato Tetsuro
Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Cancer Res. 2003 Aug 1;63(15):4407-11.
The circulating level of insulin-like growth factor-binding protein-3 (IGFBP-3) is inversely associated with the risk of prostate cancer (PCa) and its progression and may be modulated by the A/C polymorphism at position -202 in the promoter region of IGFBP-3. This study was conducted to evaluate the role of the A/C polymorphism as a genetic modifier in the etiology of PCa and its disease status. The polymorphism was analyzed by a PCR restriction fragment-length polymorphism technique in 307 PCa patients, 221 benign prostatic hyperplasia (BPH) patients, and 227 male controls. No significant difference in the genotype frequency was found between the PCa or BPH patients and controls (PCa versus control, P = 0.316; BPH versus control, P = 0.964). Regarding the tumor stage, the C allele was more frequently observed in patients having tumors with higher stage (P for trend = 0.002). When the PCa patients with localized disease (stage A + B + C) were considered as reference, those with CC and AC genotype had a significantly increased risk of metastatic disease (stage D) compared with those with AA genotype [age-adjusted odds ratio (aOR) = 3.89, 95% confidence interval (CI) = 1.42-10.64, P = 0.008, and aOR = 1.68, 95% CI = 1.01-2.79, P = 0.044, respectively]. The presence of the C allele appeared to be associated with an increased risk of metastatic PCa with a gene dosage effect (aOR = 1.82, 95% CI = 1.23-2.68, P = 0.002). Similarly, significant findings were also observed when PCa patients were compared between those with organ-confined disease (stage A + B) and those with extra-prostatic extension (stage C + D). Furthermore, the C allele was present more frequently in patients with higher tumor grade. In conclusion, the IGFBP-3 -202 A/C polymorphism was not associated with susceptibility to PCa and BPH in Japanese men, but the presence of the C allele may cumulatively increase the risk for tumor metastasis and for having tumors with a biologically more aggressive phenotype. Because of the significant differences in incidence of clinically evident PCa according to racial backgrounds, the conjecture should be further examined in different racial populations.
胰岛素样生长因子结合蛋白-3（IGFBP-3）的循环水平与前列腺癌（PCa）的风险及其进展呈负相关，并且可能受到IGFBP-3启动子区域-202位A/C多态性的调节。本研究旨在评估A/C多态性作为一种基因修饰因子在PCa病因及其疾病状态中的作用。采用聚合酶链反应-限制性片段长度多态性技术，对307例PCa患者、221例良性前列腺增生（BPH）患者和227例男性对照进行多态性分析。在PCa或BPH患者与对照之间，基因型频率未发现显著差异（PCa与对照相比，P = 0.316；BPH与对照相比，P = 0.964）。关于肿瘤分期，在肿瘤分期较高的患者中更频繁地观察到C等位基因（趋势P = 0.002）。当将局限性疾病（A + B + C期）的PCa患者作为参照时，与AA基因型患者相比，CC和AC基因型患者发生转移性疾病（D期）的风险显著增加[年龄调整优势比（aOR）= 3.89，95%置信区间（CI）= 1.42 - 10.64，P = 0.008，以及aOR = 1.68，95%CI = 1.01 - 2.79，P = 0.044]。C等位基因的存在似乎与转移性PCa风险增加以及基因剂量效应相关（aOR = 1.82，95%CI = 1.23 - 2.68，P = 0.002）。同样，当比较器官局限性疾病（A + B期）和前列腺外侵犯（C + D期）的PCa患者时，也观察到了显著结果。此外，C等位基因在肿瘤分级较高的患者中更频繁出现。总之，IGFBP-3 -202 A/C多态性与日本男性PCa和BPH的易感性无关，但C等位基因的存在可能会累积增加肿瘤转移风险以及具有生物学上更具侵袭性表型的肿瘤发生风险。由于根据种族背景临床明显PCa的发病率存在显著差异，该推测应在不同种族人群中进一步研究。
