Biomarkers of Heavy Metal Exposure Related to Pancreatic Cancer Genetic Mutations

描述(申请人提供)：胰腺癌表现出广泛的地理发病率差异，路易斯安那州湿地和密西西比河三角洲地区是美国发病率最高的地区。胰腺癌在发展中国家尚未得到广泛报道，但埃及东北部尼罗河三角洲地区是胰腺癌高发区之一。埃及和路易斯安那州提供了相似的环境环境，用于比较和可能了解胰腺癌的病因，因此，在这些地区开始初步观察后，我们建议扩大它们的范围，以调查湿地和密西西比河三角洲地区高发病率与接触镉的可能联系。我们建议对两组胰腺癌患者进行病例比较：a)路易斯安那州假定高镉暴露组，b)密歇根州假定低镉暴露组和平均胰腺癌发病率组。这项研究的第一个目的是测量来自路易斯安那州(n=50)和密歇根州(n=50)的100名胰腺癌患者的肿瘤和尿镉水平。我们将检验这一假设，即密西西比河三角洲和路易斯安那州湿地的胰腺癌患者的肿瘤和尿镉水平高于密歇根州的患者。第二个目标是进一步确定所有胰腺癌肿瘤中K-ras突变的特征。我们来自美国和埃及的初步研究结果显示，埃及镉水平高的患者中GTT K-ras突变率很高。我们将通过研究所有患者的K-ras和P53突变谱来证实我们的发现。这项研究将有助于确定路易斯安那州污染地区高组织和尿镉或其他重金属水平是否与胰腺癌风险增加有关。这项研究的结果将为胰腺癌的病因提供线索。

DESCRIPTION (provided by applicant): Pancreatic cancer shows a wide range of geographic incidence variation with Louisiana wetlands and the Mississippi delta regions having the highest rates in the U.S. Pancreatic cancer has not been widely reported in developing countries, but one area of high incidence is the northeast Nile delta region of Egypt. Egypt and Louisiana provide similar environmental settings for comparison and possible understanding of the etiology of pancreatic cancer, and thus, having begun preliminary observations in these areas, we propose to expand them to investigate possible association of elevated rates with exposure to cadmium in the wetlands and the Mississippi delta regions. We propose a case-case comparison of 2 groups of pancreatic cancer patients; a) a group experiencing presumed high cadmium exposure in Louisiana, and b) a group experiencing presumed low exposure to cadmium and average incidence of pancreatic cancer in Michigan. The first aim of the study is to measure tumor and urinary levels of cadmium in 100 pancreatic cancer patients from Louisiana (n=50) and Michigan (n=50). We will test the hypothesis that pancreatic cancer patients in the Mississippi delta and wetlands in Louisiana have higher tumor and urine cadmium levels than patients from Michigan. The second aim is to further characterize K-ras mutations in all pancreatic cancer tumors. Our preliminary findings from the U.S. and Egypt showed a high rate of GTT K-ras mutations in patients with high cadmium levels in Egypt. We will confirm our findings by characterizing the spectrum of K-ras and p53 mutations in all patients included in the proposed study. This study will help determine whether high tissue and urine cadmium or other heavy metal levels are associated with increased risk for pancreatic cancer in polluted regions in Louisiana. The results from this study will provide clues about the etiology of pancreatic cancer.