De Marzo Angelo M, DeWeese Theodore L, Platz Elizabeth A, Meeker Alan K, Nakayama Masashi, Epstein Jonathan I, Isaacs William B, Nelson William G
Department of Oncology, The Johns Hopkins University School of Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21231-1000, USA.
J Cell Biochem. 2004 Feb 15;91(3):459-77. doi: 10.1002/jcb.10747.
Prostate cancer is an increasing threat throughout the world. As a result of a demographic shift in population, the number of men at risk for developing prostate cancer is growing rapidly. For 2002, an estimated 189,000 prostate cancer cases were diagnosed in the U.S., accompanied by an estimated 30,200 prostate cancer deaths [Jemal et al., 2002]. Most prostate cancer is now diagnosed in men who were biopsied as a result of an elevated serum PSA (>4 ng/ml) level detected following routine screening. Autopsy studies [Breslow et al., 1977; Yatani et al., 1982; Sakr et al., 1993], and the recent results of the Prostate Cancer Prevention Trial (PCPT) [Thompson et al., 2003], a large scale clinical trial where all men entered the trial without an elevated PSA (<3 ng/ml) were subsequently biopsied, indicate the prevalence of histologic prostate cancer is much higher than anticipated by PSA screening. Environmental factors, such as diet and lifestyle, have long been recognized contributors to the development of prostate cancer. Recent studies of the molecular alterations in prostate cancer cells have begun to provide clues as to how prostate cancer may arise and progress. For example, while inflammation in the prostate has been suggested previously as a contributor to prostate cancer development [Gardner and Bennett, 1992; Platz, 1998; De Marzo et al., 1999; Nelson et al., 2003], research regarding the genetic and pathological aspects of prostate inflammation has only recently begun to receive attention. Here, we review the subject of inflammation and prostate cancer as part of a "chronic epithelial injury" hypothesis of prostate carcinogenesis, and the somatic genome and phenotypic changes characteristic of prostate cancer cells. We also present the implications of these changes for prostate cancer diagnosis, detection, prevention, and treatment.
前列腺癌在全球范围内构成的威胁日益增大。由于人口结构的变化，患前列腺癌风险的男性数量正在迅速增长。2002年，美国估计有189,000例前列腺癌病例被确诊，同时估计有30,200人死于前列腺癌[杰马尔等人，2002年]。现在，大多数前列腺癌是在男性因常规筛查发现血清前列腺特异抗原（PSA）水平升高（>4 ng/ml）而接受活检时被诊断出来的。尸检研究[布雷斯洛等人，1977年；矢谷等人，1982年；萨克等人，1993年]以及前列腺癌预防试验（PCPT）[汤普森等人，2003年]的最新结果表明，组织学前列腺癌的患病率远高于PSA筛查所预期的。前列腺癌预防试验是一项大规模临床试验，所有进入试验时PSA水平未升高（<3 ng/ml）的男性随后都接受了活检。环境因素，如饮食和生活方式，长期以来一直被认为是前列腺癌发生的促成因素。最近对前列腺癌细胞分子改变的研究开始为前列腺癌的发生和发展方式提供线索。例如，虽然之前有人提出前列腺炎症是前列腺癌发展的一个促成因素[加德纳和贝内特，1992年；普拉茨，1998年；德马佐等人，1999年；纳尔逊等人，2003年]，但关于前列腺炎症的遗传和病理方面的研究直到最近才开始受到关注。在这里，我们将炎症与前列腺癌这一主题作为前列腺癌发生的“慢性上皮损伤”假说的一部分进行综述，并阐述前列腺癌细胞的体细胞基因组和表型变化特征。我们还介绍了这些变化对前列腺癌诊断、检测、预防和治疗的影响。
