Genetic Epidemiology

遗传流行病学

• 批准号: 6556511
• 负责人: ALISA GOLDSTEIN
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6556511
• 关键词: European; Jewish; Wilms' tumor; autoimmune disorder; brca gene; breast neoplasms; cancer risk; clinical research; contraceptives; environmental exposure; family genetics; gene environment interaction; genetic polymorphism; genetic screening; genetic susceptibility; glioma; human data; human genetic material tag; human subject; melanoma; neoplasm /cancer epidemiology; neoplasm /cancer genetics; ovary neoplasms; patient oriented research; racial /ethnic difference; statistics /biometry

Many of the investigations in this genetic epidemiology project arise from observations in families at high risk of cancer or in other etiologic studies. Analyses of the data from a case-control study of ovarian cancer in Israel of the Jewish population revealed that parity appeared protective among both carriers and noncarriers of founder BRCA1/2 mutations. Although oral contraceptive use appeared protective among noncarriers, among carriers oral contraceptive use conferred no protection. Prognostic factors and secondary malignancies were evaluated in a retrospective study of 88 consecutive cases of childhood medulloblastoma. Overall survival was 59% at 5 years and 52% at 10 years. The risk of second neoplasms was significantly increased in this cohort of patients. Within an American case-control study of cutaneous melanoma, significant evidence for familial heterogeneity was found for melanoma. Few individuals had family members with pancreatic cancer. CDKN2A mutations were only rarely seen in this population. As a follow-up to a recently completed DCEG comprehensive case-control study of adults with brain tumors, a family-based study of the parents, siblings and adult children of the 480 eligible glioma cases is being conducted. Relatives are interviewed about personal and family medical history and other risk factors and are asked to provide buccal cells as a source of DNA. The relatives will be used as controls for the glioma cases in association studies and in analyses to evaluate the roles of genetic susceptibility and environmental exposures on the risk of gliomas and etiologically related tumors. A case-control study of 183 incident melanoma cases and 179 controls conducted in North-Eastern Italy identified the strongest risk factors for non-familial melanoma and determined how the combinations of these factors contributed to melanoma risk in Mediterranean populations. Presence of dysplastic nevi, low propensity to tan, light eye and light skin color were all highly associated with melanoma risk after adjustment for age, gender, and pigmentation characteristics. A chart showing melanoma risk associated with multiple combinations of these factors was created to identify patients who would most benefit from preventive measures in Mediterranean populations. The counter-matching design was used to examine the power for detecting gene-environment interactions. The sensitivity and specificity of the surrogate measures, the frequencies of the genetic and environmental exposures, and the value of the interaction effect were the most important parameters for determining efficiency. Feasibility was also most dependent on the exposure frequencies and interaction effect. Although still unable to study very rare factors, counter-matching appeared more appropriate than most traditional epidemiologic methods for studying interactions involving rare factors. Linked data from cancer, population, and hospital discharge registries are being obtained from collaborators in Denmark and Sweden which includes cases of lymphoproliferative (LP) cancers including Hodgkin's disease, Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, and Multiple Myeloma, matched controls, and first degree relatives of cases and controls. Hypotheses to examine increased risks of LP cancers and autoimmune disorders among relatives of cases will be tested.

这个遗传流行病学项目中的许多调查来自于对癌症高危家庭的观察或其他病因学研究。对以色列犹太人卵巢癌病例对照研究数据的分析显示，在BRCA 1/2基因突变的携带者和非携带者中，产次似乎都具有保护作用。虽然口服避孕药的使用似乎保护非运营商，运营商口服避孕药的使用没有保护。对88例儿童髓母细胞瘤的预后因素和继发性恶性肿瘤进行了回顾性研究。5年和10年的总生存率分别为59%和52%。在该患者队列中，继发肿瘤的风险显著增加。在一项美国皮肤黑色素瘤病例对照研究中，发现黑色素瘤家族异质性的重要证据。很少有人有家庭成员患有胰腺癌。CDKN 2A突变在这一人群中很少见。作为最近完成的DCEG成人脑肿瘤综合病例对照研究的后续研究，正在对480例符合条件的胶质瘤病例的父母、兄弟姐妹和成年子女进行以家庭为基础的研究。对亲属进行面谈，询问其个人和家族病史以及其他风险因素，并要求其提供口腔细胞作为DNA来源。在关联研究和分析中，亲属将被用作神经胶质瘤病例的对照，以评估遗传易感性和环境暴露对神经胶质瘤和病因相关肿瘤风险的作用。在意大利东北部进行的一项对183例偶发黑色素瘤病例和179例对照进行的病例对照研究确定了非家族性黑色素瘤的最强风险因素，并确定了这些因素的组合如何导致地中海人群的黑色素瘤风险。在调整年龄、性别和色素沉着特征后，发育不良痣、较低的晒黑倾向、浅色眼睛和浅色皮肤都与黑色素瘤风险高度相关。创建了一个图表，显示与这些因素的多种组合相关的黑色素瘤风险，以确定地中海人群中最能从预防措施中受益的患者。采用反配对设计检验检测基因-环境相互作用的功效。替代措施的灵敏度和特异性、遗传和环境暴露的频率以及相互作用效应的值是确定效率的最重要参数。可行性也主要取决于暴露频率和相互作用效应。虽然仍然无法研究非常罕见的因素，反匹配似乎比大多数传统的流行病学方法更适合研究涉及罕见因素的相互作用。从丹麦和瑞典的合作者处获得了癌症、人口和出院登记处的相关数据，其中包括淋巴增生性（LP）癌症病例，包括霍奇金病、非霍奇金淋巴瘤、慢性淋巴细胞白血病和多发性骨髓瘤、匹配对照以及病例和对照的一级亲属。将检验在病例亲属中检查LP癌症和自身免疫性疾病风险增加的假设。