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与日本散发性前列腺癌相关的HPC2/ELAC2基因多态性

HPC2/ELAC2 polymorphism associated with Japanese sporadic prostate cancer.

作者信息

Yokomizo Akira, Koga Hirofumi, Kinukawa Naoko, Tsukamoto Taiji, Hirao Yoshihiko, Akaza Hideyuki, Mori Mitsuru, Naito Seiji

机构信息

Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Prostate. 2004 Nov 1;61(3):248-52. doi: 10.1002/pros.20107.

Abstract

BACKGROUND

HPC2/ELAC2 gene was identified by linkage analysis from familial prostate cancer (Pca) patients in USA. To determine the association of HPC2/ELAC2 gene with Japanese sporadic Pca, we performed a case-control study focused on two missense polymorphisms.

METHODS

We genotyped the two polymorphic sites of Ser217Leu and Ala541Thr in sporadic Japanese Pca patients (n = 285) and matched controls (n = 233). Controls were unrelated Japanese outpatients who had no history of any cancer and normal PSA level (less than 4.0 ng/ml). Statistical analyses were performed by Mann-Whitney's U-test, Fisher's exact test, and logistic regression analysis.

RESULTS

We observed a significantly higher frequency of the Thr allele at 541 polymorphic site in Pca patients (8.4%) compared to the control group (2.1%) (P = 0.0030, Odds Ratio (OR) = 4.02, 95% CI = 1.50-10.8). However, this SNP does not correlate with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. No association was identified at Ser217Leu polymorphic site.

CONCLUSIONS

Our results indicate that Thr allele at 541 in HPC2/ELAC2 has strong significance in the predisposition of sporadic Pca in Japan. This polymorphism can be useful to predict the personal Pca risk, which lead the effective screening of Pca.

摘要

背景

HPC2/ELAC2基因是通过对美国前列腺癌(Pca)家族患者进行连锁分析而确定的。为了确定HPC2/ELAC2基因与日本散发性Pca的关联,我们针对两个错义多态性进行了一项病例对照研究。

方法

我们对日本散发性Pca患者(n = 285)和匹配的对照组(n = 233)的Ser217Leu和Ala541Thr这两个多态性位点进行了基因分型。对照组为无任何癌症病史且PSA水平正常(低于4.0 ng/ml)的无关日本门诊患者。采用曼-惠特尼U检验、费舍尔精确检验和逻辑回归分析进行统计分析。

结果

我们观察到,与对照组(2.1%)相比,Pca患者中541多态性位点的苏氨酸(Thr)等位基因频率显著更高(8.4%)(P = 0.0030,优势比(OR) = 4.02,95%置信区间 = 1.50 - 10.8)。然而,该单核苷酸多态性与临床分期、PSA水平、活检的 Gleason评分或诊断年龄无关。在Ser217Leu多态性位点未发现关联。

结论

我们的数据表明,HPC2/ELAC2基因中541位点的苏氨酸(Thr)等位基因在日本散发性Pca的易感性方面具有重要意义。这种多态性有助于预测个体患Pca的风险,从而实现对Pca的有效筛查。

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