维生素D受体、HER-2基因多态性与良性前列腺增生男性患前列腺癌的风险

Vitamin D receptor, HER-2 polymorphisms and risk of prostate cancer in men with benign prostate hyperplasia.

作者信息

Tayeb Mohammed T, Clark Caroline, Haites Neva E, Sharp Linda, Murray Graeme I, McLeod Howard L

机构信息

Department of Medical Sciences, Faculty of Medicine and Medical Sciences, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia.

出版信息

Saudi Med J. 2004 Apr;25(4):447-51.

PMID:15083213

Abstract

OBJECTIVE

Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. The vitamin D receptor (VDR) and HER-2 protooncogene have been shown to be involved in the regulation of cell proliferation and differentiation in prostate cells. Genetic variations of these genes could be useful to detect BPH patients that have a higher risk of developing PRCa. This study used a case-control design to assess the predictive value of 3 polymorphisms in VDR (TaqI and FokI) and HER-2 (Val655Ile) to determine the risk of developing PRCa in patients with BPH.

METHODS

Polymorphisms were detected by RFLP analysis. The study evaluated 28 patients who presented with PRCa at least 6 years after the diagnosis of BPH and 56 matched patients with BPH who did not progress to PRCa over a comparable period. The study was carried out in University of Aberdeen, Foresterhill, Aberdeen, United Kingdom in the year 2002.

RESULTS

Among the case group, 89% had a TT TaqI genotype, whereas 57% of control had this genotype (odds ratio [OR] = 5.16, 95% confidence interval [CI] = 1.46-18.22). A similar pattern was seen for the FokI genotype, although this was not statistically significant (OR = 2.33, 95% CI = 0.86-6.29). The frequency of the HER-2 Ile/Ile genotype was higher in cases (79%) compared to control subjects (66%), although this was not statistically significant (OR = 1.94, 95% CI = 0.67-5.63).

CONCLUSION

This study shows that the VDR TaqI polymorphism is associated with a group of men with BPH who are at an increase risk of PRCa, providing a potential tool to assist prediction strategies for this important disease.

摘要

目的

前列腺癌（PRCa）是男性癌症死亡的最常见原因之一，PRCa风险的决定因素在很大程度上仍未明确。良性前列腺增生（BPH）在大多数老年男性中都有发现，并且与PRCa有关。许多候选基因被认为与PRCa有关，例如那些对前列腺细胞生长和分化至关重要的基因。维生素D受体（VDR）和HER-2原癌基因已被证明参与前列腺细胞的增殖和分化调节。这些基因的遗传变异可能有助于检测出患PRCa风险较高的BPH患者。本研究采用病例对照设计，评估VDR基因（TaqI和FokI）和HER-2基因（Val655Ile）的3种多态性对BPH患者发生PRCa风险的预测价值。

方法

通过限制性片段长度多态性分析（RFLP）检测多态性。该研究评估了28例在诊断BPH至少6年后出现PRCa的患者，以及56例匹配的BPH患者，这些患者在相当长的时间内未进展为PRCa。该研究于2002年在英国阿伯丁福雷斯特希尔市的阿伯丁大学进行。

结果

在病例组中，89%的患者具有TT TaqI基因型，而对照组中这一基因型的比例为57%（优势比[OR]=5.16，95%置信区间[CI]=1.46-18.22）。FokI基因型也呈现出类似的模式，尽管差异无统计学意义（OR=2.33，95%CI=0.86-6.29）。病例组中HER-2 Ile/Ile基因型的频率（79%）高于对照组（66%），但差异无统计学意义（OR=1.94，95%CI=0.67-5.63）。