Family Studies

家庭研究

• 批准号: 10007394
• 负责人: Sharon A. Savage
• 金额: $ 114.89万
• 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/10007394
• 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 structure; 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部的调查评估宿主易感性和环境暴露在癌症发展中的作用。在家庭研究中，宿主的易感性测量通常是特定基因的改变。这些研究往往是长期的，有不同的活动。虽然已经确定了两个与黑色素瘤易感性相关的基因（CDKN2A和CDK4），但这些基因的改变仅在一小部分易患黑色素瘤的家族中被发现。对其他基因的研究仍在继续；与国际联盟（GenoMEL）合作，继续在家族和全基因组关联研究中寻找新的黑色素瘤易感基因。在美国和意大利黑色素瘤易发家族中，我们正在使用包括阵列比较基因组杂交（aCGH）和下一代测序（外显子组和全基因组）在内的新技术来寻找新的高危黑色素瘤易感基因。在过去的一年里，我们在意大利和美国家庭中发现了另一个高危易感基因POT-1。我们继续在美国、意大利和西班牙积累和评估新的家庭。我们继续评估遗传性视网膜母细胞瘤和黑色素瘤个体的家庭。我们正在对发展为第二恶性肿瘤的视网膜母细胞瘤幸存者进行外显子组测序。家族性脊索瘤是一种罕见的、低级别的恶性骨肿瘤，起源于脊索的残余，其研究已扩展到其他家族。虽然我们已经报道了T基因的重复（短链）是家族性脊索瘤的主要遗传风险因素，但一些家庭并没有T基因异常。我们正在对未确定高危易感基因的家族进行下一代外显子组测序。研究淋巴增生性癌症的家族一直是一个长期的兴趣。我们与CLL遗传流行病学联盟合作，对家族性CLL进行更大规模的研究。我们正在使用外显子组和全基因组测序来寻找CLL、HD、WM和NHL家族的高危易感基因。我们还与CCR研究人员合作，继续对着色性干皮病进行家族研究，以评估XP杂合子的癌症风险。数据收集仍在继续。