ALTERED IMMUNE/INFLAMMATORY PATHWAY IN RACIALLY DIVERSE PROSTATE CANCERS

前列腺癌是老年男性发病率和死亡率的主要原因。雄激素受体(AR) 前列腺上皮(PE)细胞中雄激素的表达和反应(通路)是决定 PCA。有趣的是，在PE内存在强烈的雄激素调节的免疫/炎症信号。 细胞。在正常PE中，雄激素促进抗肿瘤急性炎症和抑制亲肿瘤的慢性 炎症途径。因为前列腺炎是已知的前列腺癌最早的先兆 因此，参与调节雄激素依赖的基因的表达或遗传差异发生变化 炎症/免疫反应可能是前列腺癌发生的危险因素。这些能不能 雄激素调节的免疫/炎症途径中的遗传差异也解释了 非裔美国人男性前列腺癌的发病率更高？为了解决这个问题，我们建议“” 观察到前列腺癌发病率的种族差异是由于基因表达的差异。 一组雄激素调控的免疫/炎症途径内的多态性及其基因 该通路可作为不同种族前列腺癌的有效预后标志物 结果将证明雄激素依赖的炎症性/ 免疫反应途径可导致局部(前列腺)免疫反应受损，从而预先准备 对PCa或在获得雄激素非依赖性后，促进侵袭性PCa的发展 非裔美国人。该项目将分析以下基因集的表达：急性：IFNG、IFNA、MX1、 OAS1、PKR、CXCL10和慢性：IL6、JunB、CEBPD、gp130。此外，还对中国的特定SNP进行了分析 还提出了IFNG、IL6、OAS1、MX1和PKR。样本将由正常前列腺和前列腺组成。 取自非裔美国人和高加索人的癌症组织。豌豆和豌豆的发病率最高 世界上的死亡率是在非裔美国人中。免疫/炎症的变化 途径因表达下调或遗传多态可提供较高的分子基础 非洲裔美国男性的前列腺癌发病率。拟议的研究将涉及这些分子 机械装置。因此，了解这些癌症的危险因素对预后具有实际意义。 公共卫生努力、遗传和营养教育以及开发更好的治疗方案。

Prostate cancer (Pea) is a major cause for morbidity and mortality in aging men. Androgen receptor (AR) expression and response to androgens (pathways) in prostate epithelial (PE) cells are key determinants of PCa. Interestingly, there exists a strong androgen regulated immune/ inflammatory signature within the PE cells. In the normal PE, androgens promote anti-tumor acute inflammation and suppress pro-tumor chronic inflammation pathway. Since inflammation of the prostate is the earliest known precursor of prostate cancer therefore altered expression or genetic differences in the genes involved in mediating androgen dependent inflammatory/ immune response can be a risk factor for the development of prostate cancer. Can these genetic differences within the androgen regulated immune/ inflammatory pathways also account for the higher incidence of PCa in African American men? In order to address this question we propose that ""The observed racial disparity in prostate cancer incidence is due to genetic differences in the expression/ polymorphism within a group of androgen regulated immune/ inflammatory pathway and that the genes within this pathway can be used as effective prognostic markers of prostate cancer in racially diverse populations". The results will demonstrate that the perturbations in the androgen dependent inflammatory/ immune response pathway can lead to a locally (prostate) compromised immune response that pre-disposes to PCa or following acquisition of androgen independence, promotes the development of aggressive PCa in African Americans. The project will analyze expression of the following gene set: Acute: IFNG, IFNA, MX1, OAS1, PKR, CXCL10 and Chronic : IL6, JUNB, CEBPD, GP130. In addition analysis of specific SNPs in IFNG, IL6, OAS1, MX1 and PKR is also proposed. The samples will consist of normal prostate and prostate cancer tissue obtained from African-American and Caucasian men. The highest incidence rates for Pea and mortality in the world are among African-American men. The alterations in the immune/ inflammatory pathway due to de-regulated expression or genetic polymorphism can provide the molecular basis of higher prostate cancer incidence in African-American men. The proposed studies will address these molecular mechanisms. An understanding of these risk factors for cancer thus has practical importance for prognosis, public health efforts, genetic and nutritional education and developing better treatment regimens.