GENETIC EPIDEMIOLOGY AND MOLECULAR PATHOLOGY OF COLORECTAL CANCER IN HISPANICS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的总体目标是为西班牙裔结直肠癌的预防，诊断和治疗制定一个范例。 这项试点研究是探索西班牙裔结直肠癌发生途径的第一步，将为未来研究西班牙裔结直肠癌相关的发病机制，分子生物学和遗传流行病学奠定基础。结肠直肠肿瘤的流行病学和分子遗传学已被充分了解，并且已知存在国际人群差异。 结直肠癌是美国癌症死亡的第二大常见原因。在波多黎各，结肠直肠癌是第二大常见的癌症病因，每年影响约1，500人，占该岛所有癌症病例的12%。 文献中关于波多黎各结直肠癌的报道很少。因此，很少有人知道的遗传概况和遗传流行病学的结直肠癌患者在波多黎各。该提案将调查结直肠癌中报告的一些最常见的遗传变化，以评估其在西班牙裔患者中的频率。将追求以下具体目标：（1）确定波多黎各西班牙裔结直肠癌患者在UPRCC治疗的患者的人口统计学和临床病理学特征方面的遗传流行病学;（2）通过自动分析二核苷酸和单核苷酸重复序列的移位，确定微卫星不稳定性的流行率，在UPRCC接受治疗的波多黎各西班牙裔结直肠癌患者;（3）检测错配修复基因蛋白的表达（hMSH2、hMLH1、hMSH6、hPMS2），和在UPRCC治疗的波多黎各西班牙裔结直肠癌患者的hMLH 1启动子甲基化。了解西班牙裔人潜在的结直肠癌分子改变可能有助于制定新的预防，检测和治疗策略，最终减少这种疾病的负担。 这项试点调查将为我们提供关于波多黎各西班牙裔患者中CRC遗传流行病学的初步数据，这将是未来调查和建议的基础，以确保校外资金。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our overall goal is to develop a paradigm for the prevention, diagnosis, and treatment of colorectal cancer among Hispanics. This pilot study represents the first step to explore the pathways involved in the carcinogenesis of colorectal cancer among Hispanics and will lay the foundation for future investigations into the pathogenesis, molecular biology, and genetic epidemiology relevant to Hispanics with colorectal cancer. The epidemiology and molecular genetics of colorectal neoplasia are well understood, and international population differences are known to occur. Colorectal cancer is the second most common cause of cancer deaths in the United States. In Puerto Rico, colorectal cancer is the second most common cause of cancer affecting approximately 1,500 individuals annually, which represents 12% of all cancer cases in the island. There has been a paucity of reports in the literature regarding colorectal cancer in Puerto Rico. Thus, little is known about the genetic profile and the genetic epidemiology of colorectal cancer in Puerto Rican patients. This proposal will investigate some of the most common genetic changes reported in colorectal cancer to assess their frequency in Hispanic patients. The following specific aims will be pursued: (1) To determine the genetic epidemiology of Puerto Rican Hispanic colorectal cancer patients with regards to demographic and clinicopathologic features for patients treated at the UPRCC; (2) To determine the prevalence of microsatellite instability, determined by automated analysis of shifts in dinucleotide and mononucleotide repeat sequences, for Puerto Rican Hispanic colorectal cancer patients treated at UPRCC; (3) To determine the prevalence of mismatch repair genes' protein expression (hMSH2, hMLH1, hMSH6, hPMS2), determined by immunohistochemisty, and hMLH1 promoter methylation for Puerto Rican Hispanic colorectal cancer patients treated at UPRCC. Understanding the underlying colorectal cancer molecular alterations in Hispanics may perhaps facilitate the development of new strategies for prevention, detection, and treatment that could ultimately decrease the burden of this disease. This pilot investigation will give us preliminary data about the genetic epidemiology of CRC in Puerto Rican Hispanics in a well-characterized cohort of patients, which will be the foundation for future investigations and proposals to secure extramural funding.