Gonzalgo Mark L, Isaacs William B
James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
J Urol. 2003 Dec;170(6 Pt 1):2444-52. doi: 10.1097/01.ju.0000085381.20139.b6.
Prostate cancer continues to be a prevalent disease in the United States and western countries. Advances in the fields of molecular biology and genetics coupled with new developments in biotechnology have increased our understanding of events associated with the initiation and progression of prostate cancer. We reviewed recent scientific discoveries relating to genetic predisposition, somatic alterations and epigenetic phenomena involved in the pathogenesis of prostate cancer.
Reports published in the scientific literature with relevance to the molecular biology, genetics and epigenetics of prostate cancer were identified using the MEDLINE data base. Particular emphasis was placed on articles that investigated the contribution of somatic alterations to prostate cancer.
A multitude of genes have recently been identified that are believed to be relevant to prostate carcinogenesis. A contemporary model for prostate cancer progression should include the potential contribution of inflammation to the development of preneoplastic or neoplastic lesions. Abnormal methylation of important growth regulatory or caretaker genes represents an alternative pathway to cancer in addition to aneuploidy, loss of heterozygosity and gene mutations.
The identification of molecular markers specific to early and late events in prostate cancer progression is critical for the development of improved detection and prognostication strategies. While there is evidence to support the association between inflammation and prostate cancer, the exact mechanisms by which these processes occur are not well defined. The significant contribution of somatic and epigenetic defects to prostate carcinogenesis underscores the need to develop therapeutic approaches that specifically target these molecular alterations.
前列腺癌在美国和西方国家仍然是一种常见疾病。分子生物学和遗传学领域的进展，以及生物技术的新发展，加深了我们对与前列腺癌发生和发展相关事件的理解。我们综述了近期与前列腺癌发病机制中遗传易感性、体细胞改变和表观遗传现象相关的科学发现。
使用MEDLINE数据库检索科学文献中与前列腺癌分子生物学、遗传学和表观遗传学相关的报告。特别强调了研究体细胞改变对前列腺癌影响的文章。
最近发现了许多被认为与前列腺癌发生相关的基因。一个当代的前列腺癌进展模型应包括炎症对癌前或肿瘤性病变发展的潜在影响。重要生长调节基因或维持基因的异常甲基化除了非整倍体、杂合性缺失和基因突变外，代表了另一条致癌途径。
识别前列腺癌进展中早期和晚期事件的特异性分子标志物对于改进检测和预后策略的发展至关重要。虽然有证据支持炎症与前列腺癌之间的关联，但这些过程发生的确切机制尚未明确。体细胞和表观遗传缺陷对前列腺癌发生的重大影响凸显了开发针对这些分子改变的治疗方法的必要性。
