PATERNAL EXPOSURE AND SPORADIC BILATERAL RETINOBLASTOMA

描述：我们建议进行一项散发性肺炎的分子流行病学研究。 遗传性视网膜母细胞瘤(RBL)，一种发生于 婴幼儿。我们对分子事件的了解导致了 散发性可遗传RBL和疾病的某些特征共同提供了一种 为这项研究提供了难得的机会。在拟议的研究中，我们将调查 散发性可遗传RBL本身，并作为新生殖系的模型 突变。 散发性可遗传RBL源于RBL基因的一种新的生殖系突变， 在超过90%的案例中，这种情况发生在父亲的基因上。这项研究的 主要目的是调查父亲的职业，饮食， 在孩子怀孕前接触X光和烟草。由于RBL基因 我们将进行分子遗传分析，以确定 所有病例中都有突变。突变数据将与曝光一起使用 检验电离辐射和父亲年龄较大是危险的假设的数据 导致特定类型突变的因素。 本研究将采用配对病例对照设计，共250对。案件将会是 通过治疗大多数RBL患者的七个中心确定 美国和加拿大。控制将通过随机数字拨号和 与出生日期、种族和地理区域相匹配。电话采访 将与病例和对照的父母一起进行。血液样本将会是 从病例和病例父母那里获得，这样就可以分离DNA进行突变 分析。 拟议的分子流行病学研究将提供有关 散发性遗传性视网膜母细胞瘤的病因学。这项研究还将 有助于我们对新的生殖系突变的了解，关于 人们对此知之甚少。散发性遗传性RBL是一种儿童癌症 自学成才是新文学研究的理想模式 生殖系突变。

DESCRIPTION: We propose to conduct a molecular epidemiologic study of sporadic heritable retinoblastoma (RBL), a cancer of the embryonal retina that occurs in infants and young children. Our knowledge of the molecular events leading to sporadic heritable RBL and certain features of the disease together provide a unique opportunity for this study. In the proposed study, we will investigate sporadic heritable RBL in its own right and as a model for new germline mutation. Sporadic heritable RBL results from a new germline mutation in the RBL gene, which occurs on the father's gene in over 90 percent of cases. The study's major objectives are to investigate the role of paternal occupational, dietary, x-ray and tobacco exposures before the child's conception. Since the RBL gene is well characterized, we will do molecular genetic analyses to identify the mutation in all of the cases. The mutation data will be used with the exposure data to test hypotheses that ionizing radiation and older paternal age are risk factors for specific types of mutation. The study will use a matched case-control design with 250pairs. Cases will be ascertained through seven centers that treat most of the RBL patients in the U.S. and Canada. Controls will be identified by random-digit dialing and matched to cases on birth date, race, and geographic area. Telephone interviews will be conducted with parents of cases and controls. Blood samples will be obtained from cases and case parents, so that DNA can be isolated for mutation analysis. The proposed molecular epidemiologic study will provide new information about the etiology of sporadic heritable retinoblastoma. The study will also contribute to our knowledge of new germline mutation generally, about which very little is known. Sporadic heritable RBL is a childhood cancer worth studying in its own right and an ideal model for the investigation of new germline mutation.