Family Studies

大多数遗传流行病学分支研究评估宿主易感性和环境暴露在癌症发展中的作用。在家系研究中，宿主易感性的测量通常是特定基因的改变。这些研究往往是非常长期的，具有不同的活动。虽然已经确定了与黑色素瘤易感性相关的两个基因（CDKN 2A和CDK 4），但这些基因的改变仅在一小部分黑色素瘤易感家族中发现。对其他基因的研究仍在继续;与国际财团（GenoMEL）合作，在家族和全基因组关联研究中继续寻找新的黑色素瘤易感基因。在美国和意大利的黑色素瘤易感家族中，我们正在使用新的技术，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），以寻找新的高风险黑色素瘤易感基因。在过去的一年里，我们在意大利和美国的家庭中发现了另一个高危易感基因POT-1。我们继续在美国和美国评估新的家庭，意大利和西班牙。我们继续评估遗传性视网膜母细胞瘤和黑色素瘤患者的家族。我们正在进行外显子组测序的视网膜母细胞瘤幸存者谁开发了第二恶性肿瘤。家族性脊索瘤是一种罕见的、低度恶性的骨肿瘤，起源于脊索的残余，其研究被扩大到包括其他家族。虽然我们曾报道T基因重复（短尾畸形）是家族性脉络膜炎的主要遗传危险因素，但有几个家族并没有T基因异常。 我们正在对未发现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庭一直是一个长期的兴趣。我们与CLL联盟的遗传流行病学合作，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家族中的高危易感基因。我们还继续与CCR研究人员合作进行着色性干皮病的家族研究，以评估XP杂合子的癌症风险。继续收集数据。

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.