Biomarkers of Heavy Metal Exposure Related to Pancreatic Cancer Genetic Mutations

与胰腺癌基因突变相关的重金属暴露生物标志物

• 批准号: 7283033
• 负责人: Amr Soliman
• 金额: $ 7.32万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7283033
• 关键词: Accounting; Adenocarcinoma; Area; Asian Americans; Biological Markers; Cadmium; Cancer Etiology; Cancer Patient; Cause of Death; Cessation of life; Characteristics; Developed Countries; Developing Countries; Diagnosis; Disease; Egypt; Environmental Exposure; Environmental and Occupational Exposure; Epidemiology; Ethnic group; Etiology; Exons; Exposure to; Future; Gene Mutation; Genes; Grant; Heavy Metals; Hispanics; Hospital Referrals; Incidence; Investigation; Life Style; Louisiana; Malignant Neoplasms; Malignant neoplasm of pancreas; Mass Spectrum Analysis; Measures; Metal exposure; Michigan; Mississippi; Molecular; Mutation; Newly Diagnosed; Not Hispanic or Latino; Pancreas; Pancreatic duct; Participant; Pathologic; Patients; Population; Predisposition; Quality of life; Range; Rate; Recording of previous events; Reporting; Risk; Rivers; Staging; Symptoms; TP53 gene; Testing; Time; Tissues; Tumor Tissue; United States; Unresectable; Urine; Variant; Woman; cancer genetics; carcinogenesis; comparison group; experience; men; mortality; pancreatic neoplasm; tumor; urinary

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.

描述（由申请人提供）：胰腺癌具有广泛的地理发病率差异，其中路易斯安那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，但埃及的尼罗河三角洲东北部地区是一个高发地区。埃及和路易斯安那州提供了类似的环境条件，用于比较和可能了解胰腺癌的病因，因此，在这些地区开始了初步观察，我们建议扩大它们，以调查湿地和密西西比三角洲地区镉暴露与发病率升高的可能联系。我们提出两组胰腺癌患者的病例比较；a)路易斯安那州假定镉暴露量高的一组；b)密歇根州假定镉暴露量低且胰腺癌平均发病率高的一组。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中的镉水平。我们将检验一个假设，即密西西比三角洲和路易斯安那湿地的胰腺癌患者的肿瘤和尿液中的镉含量高于密歇根州的患者。第二个目标是进一步表征所有胰腺癌肿瘤中的K-ras突变。我们从美国和埃及的初步调查结果显示，在埃及高镉水平的患者中，GTT K-ras突变的发生率很高。我们将通过对纳入研究的所有患者的K-ras和p53突变谱进行表征来证实我们的发现。这项研究将有助于确定高组织和尿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。这项研究的结果将为胰腺癌的病因提供线索。