Cadmium, K-ras, and Pancreatic Cancer in Egypt

描述(由申请人提供)： 胰腺癌是一种致命的疾病，它很快就会剥夺患者的生活质量和数量。它是美国癌症死亡的第五大原因。2001年，估计有29,200例新病例被诊断，28,900人死于这种疾病。胰腺癌的中位生存期为6个月，确诊后只有4%的患者存活5年。鉴于其发病率和几乎全部死亡，显然有必要加大研究力度，以了解、预防和控制这种疾病。 虽然胰腺癌在发展中国家包括埃及大部分地区是罕见的，但埃及尼罗河三角洲东北部地区为研究胰腺癌提供了独特的环境，因为：1)该地区有大量的胰腺癌病例；2)该地区居民的血清镉水平较高；以及3)该地区患者胰腺癌的独特分子病理特征[GGT-&&GT；GTT(甘氨酸--&GT；valine)K-ras突变]。 镉一直被怀疑是胰腺癌的致癌物，在这一人群中，除了肿瘤独特的K-ras突变外，大量病例和早发性疾病可能是由高镉暴露引起的。我们提出了一项初步研究，以产生一种假设，即在这一人群中，胰腺癌是由高水平暴露于环境镉引起的。我们将招募150名胰腺癌对照人员和150名年龄、性别和居住地匹配的医院对照人员。我们将研究终生流行病学、环境和癌症家族史，以确定新的环境或生活方式相关因素，预测在高不良环境暴露人群中患胰腺癌的风险。我们还将检测病例和对照组的血镉水平以及肿瘤患者的K-ras突变类型，以确定这种独特的突变类型是否与较高的血镉水平或其他环境暴露有关。这项研究可能明确镉在胰腺癌病因学中的作用，并可能为未来胰腺癌流行病学中基因-环境相互作用的研究奠定基础。

DESCRIPTION (provided by applicant): Pancreatic cancer is a lethal disease that quickly deprives patients of both quality and quantity of life. It is the fifth leading cause of cancer death in the United States. In 2001, an estimated 29,200 new cases were diagnosed, and 28,900 people died from the disease. The median survival of pancreatic cancer is six months and only 4% of patients are alive five years after diagnosis. Given its incidence and almost entire fatality, substantially increased research efforts are clearly warranted to understand, prevent, and control this disease. Although pancreatic cancer is rare in developing countries, including most of Egypt, the northeast Nile Delta region of Egypt offers a unique setting for studying pancreatic cancer because of: 1) its large number of pancreatic cancer cases; 2) the high serum cadmium levels in residents of the region; and 3) the unique molecular pathologic features of pancreatic cancer tumors of patients from this region [unusually high rate of GGT --> GTT (glycine --> valine) K-ras mutation]. Cadmium has been suspected as a carcinogen for pancreatic cancer and the large number of cases and early-onset disease in addition to the unique K-ras mutations of tumors in this population may be caused by high cadmium exposures. We propose a pilot study to generate a hypothesis that pancreatic cancer, in this population, is caused by high levels of exposure to environmental cadmium. We will recruit 150 pancreatic cancer controls and 150 age-, sex- and residence-matched hospital controls. We will examine lifetime epidemiologic, environmental and cancer family histories to identify novel environmental or lifestyle-related factors that predict risk for pancreatic cancer in this population with high adverse environmental exposures. We will also test serum cadmium levels in cases and controls and K-ras mutation types in tumors of cases to define if the unique mutation types are associated with higher serum cadmium levels or other environmental exposures. This study may define the role of cadmium in the etiology of pancreatic cancer and may set the stage for future studies on gene-environmental interactions in the epidemiology of pancreatic cancer.