PREMALIGNANT LESIONS OF THE PROSTATE--AGE AND RACE STUDY

前列腺癌前病变——年龄和种族研究

• 批准号: 2443199
• 负责人: WAEL A. SAKR
• 金额: $ 29.64万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-13 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2443199
• 关键词: DNA; age difference; aneuploidy; angiogenesis; cell cycle; cell differentiation; histopathology; human genetic material tag; human middle age (35-64); human subject; neoplasm /cancer epidemiology; prostate; prostate preneoplastic state; racial /ethnic difference; tumor suppressor genes

Prostatic carcinoma (PCa) is the most commonly diagnosed malignancy in American males and is responsible for 13% of all male cancer-related deaths. African-American (AA) males have a 50% higher incidence and suffer twice the mortality rates due to this cancer compared to Caucasians (C). The reason(s) for this difference are not known. PCa can be viewed as encompassing two major forms. Latent cancers, defined as those found incidently in men without clinical evidence of having PCa, are extremely prevalent, can be identified as early as the third decade of life and show no documented racial difference in prevalence. Clinical cancers, defined as those which have come to clinical attention, are significantly less common than latent PCa, show variable rates of progression and are associated with geographic, ethnic and racial differences in incidence and mortality. Precursors of PCa are poorly defined. A morphologically well characterized entity termed high grade prostatic intraepithelial neoplasia (HGPIN) has shown strong epidemiologic association with the clinically diagnosed form of PCa. Our data has shown HGPIN to be more prevalent in AA than C males between 30 and 70+ years of age. Furthermore, extensive HGPIN diffusely involving the gland is more common in AA than C males of the same ages with extensive HGPIN appearing about a decade earlier in AA than C males. We have also observed a lack of anatomic association between HGPIN and the majority (67%) of latent PCa in young men (under age 5)) of both races. The significantly higher incidence of clinical PCa in AA men with similar prevalence of latent PCa indicates that some other factor(s) are responsible for this clinical discrepancy. Two possible explanations are that (1) HGPIN is more common and extensive in AA males and is genetically unstable as compared to C men, and 2) that a higher proportion of latent PCa anatomically related to HGPIN in AA men may be more likely to progress to a clinically manifest disease. These hypotheses will be tested using conventional whole mount histopathology performed on step-sectioned entire prostate glands. That HGPIN is more extensive in AA compared to C males in the age group of 50- 65 years, the time span preceding clinically diagnosed PCa will be confirmed. The more extensive HGPIN in AA will be evaluated for greater genetic instability by studying the frequency of loss of a tumor suppressor gene located on the short arm of chromosome 8 (8p22). The loss of this locus has been documented to be a frequent event in prostatic carcinogenesis. Biological markers of tumor aggressiveness such as larger volume, less differentiated histology, aneuploid tumor DNA content and higher rates of proliferation and angiogenic activity will also be studied. It is expected that the valuation of these parameters in AA and C men will provide strong support for the hypothesis presented and will lead to a greater understanding of the observed epidemiological differences in PCa between races.

前列腺癌（PCa）是最常见的恶性肿瘤 美国男性 13% 的男性癌症与此有关 死亡人数。 非裔美国 (AA) 男性的发病率高出 50%， 与白人相比，这种癌症的死亡率是白人的两倍 （三）。 造成这种差异的原因尚不清楚。 可以查看PCa 包括两种主要形式。 潜伏癌症，定义为发现的癌症 顺便说一句，在没有临床证据表明患有 PCa 的男性中， 普遍存在，早在生命的第三个十年就可以识别并表现出来 没有记录在患病率方面存在种族差异。 临床癌症的定义 因为那些已经引起临床关注的疾病明显较少 比潜伏性 PCa 更常见，表现出不同的进展速度，并且 与发病率的地理、民族和种族差异有关 死亡。 PCa 前体的定义不明确。 形态上良好 称为高级别前列腺上皮内瘤变的特征实体 （HGPIN）已显示出与临床的强烈流行病学关联 诊断出的 PCa 形式。 我们的数据显示 HGPIN 在以下领域更为普遍： 30岁至70岁以上男性中AA多于C。 此外，广泛 HGPIN 弥漫性累及腺体在 AA 男性中比 C 男性中更常见 年龄相同，广泛的 HGPIN 大约早十年出现在 AA 中 比 C 男。 我们还观察到缺乏解剖学关联 HGPIN 与年轻男性（年龄以下）中大多数 (67%) 的潜在 PCa 之间的关系 5)) 两个种族。 具有相似症状的 AA 男性临床 PCa 发生率显着更高 潜伏性 PCa 的患病率表明还有一些其他因素 造成这种临床差异的原因。 两种可能的解释是 (1) HGPIN 在 AA 男性中更为常见和广泛，并且与遗传有关 与 C 人相比不稳定，2）潜在的比例更高 在 AA 男性中，在解剖学上与 HGPIN 相关的 PCa 可能更有可能进展 到有临床表现的疾病。 这些假设将使用传统的整体安装进行测试 对整个前列腺的阶梯切片进行组织病理学。 那 与 50-50 岁年龄组的 C 男性相比，HGPIN 在 AA 男性中更为广泛 65 年，临床诊断出 PCa 之前的时间跨度将为 确认的。 AA 中更广泛的 HGPIN 将得到更大的评估 通过研究肿瘤丢失的频率来研究遗传不稳定性 抑制基因位于8号染色体短臂(8p22)。 损失 该位点已被记录为前列腺中的常见事件 致癌作用。 肿瘤侵袭性的生物标志物，例如较大的 体积、低分化组织学、非整倍体肿瘤 DNA 含量和 更高的增殖率和血管生成活性也将 研究过。 预计 AA 和 中这些参数的估值 C 人将为所提出的假设提供强有力的支持，并将 有助于更好地了解观察到的流行病学 种族之间 PCa 的差异。