Family Studies

家庭研究

• 批准号: 10702899
• 负责人: Sharon A. Savage
• 金额: $ 399.27万
• 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/10702899
• 关键词: American; Brachyury protein; Brain; Breast; Bronchi; CCR; CDK4 gene; CDKN2A gene; Categories; Childhood; Chordoma; Chronic Lymphocytic Leukemia; Collaborations; Data Collection; Development; Disease; Educational Materials; Environmental Exposure; Family; Family Study; Family health status; Family member; Genes; Genotype; Goals; Health Professional; Hereditary Malignant Neoplasm; Heritability; Heterozygote; Hodgkin Disease; Individual; International; Intervention; Investigation; Italy; Lesion; Lung; Malignant Bone Neoplasm; Malignant Neoplasms; Measures; Natural History; Nervous System; Non-Hodgkin' s Lymphoma; Penetrance; Phenotype; Pleura; Predisposition; Reporting; Research Personnel; Retinoblastoma; Risk; Second Primary Neoplasms; Skin Carcinoma; Spain; Survivors; Susceptibility Gene; Trachea; Tumor-Derived; Waldenstrom Macroglobulinemia; Xeroderma Pigmentosum; cancer risk; comparative genomic hybridization; exome sequencing; gene environment interaction; genetic epidemiology; genetic risk factor; genome sequencing; genome wide association study; high risk; interest; melanoma; mutation carrier; new technology; next generation; next generation sequencing; notochord; rate of change; whole genome

Most Genetic Epidemiology Branch investigations evaluate the contributions of host susceptibility and environmental exposure in the development of cancer. In family studies, the host susceptibility measure is frequently an alteration in specific gene(s). These studies tend to be very long term with varying activity. Although two genes associated with melanoma susceptibility have been identified (CDKN2A and CDK4), alterations in these genes are found in only a small percentage of melanoma-prone families. The search for other genes continues; in collaboration with an international consortium (GenoMEL), a search for new melanoma susceptibility genes continues both within families and genome-wide association studies. In the American and Italian melanoma-prone families, we are using novel technologies including array comparative genomic hybridization (aCGH) and next generation sequencing (exomic and whole genome) to search for new high-risk melanoma susceptibility genes. In the past year, we have found another high-risk susceptibility gene, POT-1 in Italian and American families. We continue to accrue and evaluate new families in both the U.S., Italy, and Spain. We have continued to evaluate families of individuals with heritable retinoblastoma and melanoma. We are conducting exome sequencing in retinoblastoma survivors who have developed second malignancies. The study of familial chordoma, a rare, low-grade, malignant bone tumor derived from remnants of the notochord, was expanded to include additional families. Although we have reported duplications of the T gene (brachyury) as a major genetic risk factor for familial chordoma, several families do not have abnormalities in the T gene. We are conducting next generation exomic sequencing in the families without identified high risk susceptibility genes. Studying families with lymphoproliferative cancers has been a long-standing interest. We have collaborated with the Genetic Epidemiology of CLL Consortium to conduct larger studies of familial CLL. We are using exomic and whole genome sequencing to search for high risk susceptibility genes in CLL , HD, WM, and NHL families. We also continued a family study of Xeroderma pigmentosum in collaboration with CCR investigators to assess risk of cancer in XP heterozygotes. Data collection continues.

大多数遗传流行病学分支研究都评估了宿主易感性和环境暴露在癌症发展中的贡献。在家庭研究中，宿主易感性度量通常是特定基因的改变。这些研究往往很长，活动的活动变化。尽管已经鉴定出了两个与黑色素瘤易感性相关的基因（CDKN2A和CDK4），但仅在一小部分容易发生黑色素瘤的家族中发现了这些基因的改变。寻找其他基因的搜索仍在继续；与国际财团（Genomel）合作，在家庭和全基因组关联研究中，寻找新的黑色素瘤敏感性基因仍在继续。在美国和意大利黑色素瘤家族中，我们正在使用新型技术，包括阵列比较基因组杂交（ACGH）和下一代测序（外部和整个基因组）来寻找新的高风险黑色素瘤敏感性基因。在过去的一年中，我们在意大利和美国家庭中发现了另一个高风险敏感性基因，pot-1。我们继续在美国，意大利和西班牙进行累积和评估新家庭。我们继续评估具有遗传性视网膜细胞瘤和黑色素瘤的个体家庭。我们正在发生第二次恶性肿瘤的视网膜母细胞瘤幸存者中进行外显子组测序。对家族性脊全瘤的研究是一种稀有的，低级的恶性骨肿瘤，衍生自脊索的残余物，扩展到包括其他家庭。尽管我们报告了T基因（Brachyury）作为家族脊髓瘤的主要遗传危险因素的重复，但几个家族在T基因中没有异常。 我们正在家庭中进行下一代外观测序，但未识别出高风险敏感性基因。 研究淋巴增生性癌症的家庭一直是一个长期的兴趣。我们已经与CLL联盟的遗传流行病学合作，以进行大型家族性CLL研究。我们正在使用Exomic和整个基因组测序来寻找CLL，HD，WM和NHL家族中的高风险敏感性基因。我们还与CCR研究人员合作，继续一项针对XP杂合子癌的风险的小心排骨色素研究的家庭研究。数据收集仍在继续。