Biomarkers of Heavy Metal Exposure Related to Pancreatic Cancer Genetic Mutations

描述（由申请人提供）：胰腺癌显示出广泛的地理发病率变化，路易斯安那州湿地和密西西比三角洲地区在美国发病率最高。胰腺癌在发展中国家尚未广泛报道，但一个高发地区是埃及的东北尼罗河三角洲地区。埃及和路易斯安那州提供了类似的环境设置的比较和可能的了解胰腺癌的病因，因此，已经开始在这些地区的初步观察，我们建议扩大他们调查可能的关联率升高与暴露于镉的湿地和密西西比三角洲地区。我们建议对两组胰腺癌患者进行病例-病例比较; a）路易斯安那州的一组患者经历了假定的高镉暴露，B）密歇根州的一组患者经历了假定的低镉暴露和胰腺癌平均发病率。该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液镉水平。我们将检验一个假设，即在密西西比三角洲和路易斯安那州湿地的胰腺癌患者比密歇根州的患者有更高的肿瘤和尿镉水平。第二个目的是进一步表征所有胰腺癌肿瘤中的K-ras突变。我们在美国和埃及的初步研究结果显示，在埃及高镉水平的患者中，GTT K-ras突变率很高。我们将通过描述所有纳入本研究的患者的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高组织和尿液镉或其他重金属水平是否与路易斯安那州污染地区胰腺癌风险增加有关。本研究的结果将为胰腺癌的病因学提供线索。

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.