Family Studies

大多数遗传流行病学分支调查评估宿主易感性和环境暴露在癌症发生中的作用。在家族性研究中，宿主的易感性指标通常是特定基因的改变(S)。这些研究往往是非常长期的，活动各不相同。虽然已经发现了两个与黑色素瘤易感性相关的基因(CDKN2A和CDK4)，但在黑色素瘤易感家族中只有一小部分发现了这些基因的变化。对其他基因的搜索仍在继续；与一个国际联盟(GenMEL)合作，继续在家族内和全基因组关联研究中寻找新的黑色素瘤易感基因。在美国和意大利的黑色素瘤易感家族中，我们正在使用包括阵列比较基因组杂交(ACGH)和下一代测序在内的新技术来寻找新的高危黑色素瘤易感基因。我们继续在美国和意大利招募和评估新家庭。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庭。家族性脊索瘤是一种罕见的、低级别的恶性骨肿瘤，来源于脊索残留物，研究范围扩大到包括更多的家族。最近，我们使用阵列CGH来确定T基因(Brachyury)的复制，它在无索发育中起重要作用，并且在大多数散发性脊索瘤中表达，在四个多重脊索瘤家族的成员中与脊索瘤共分离。这是第一个基因复制导致主要家族对癌症易感性的例子。我们目前正在使用外显子组测序在没有T基因重复的脊索瘤家族中寻找致病突变。对淋巴增殖性癌症家族的研究一直是人们的兴趣所在。我们已经与CLL联盟的遗传流行病学合作，对家族性CLL进行了更大规模的研究。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。我们还与CCR研究人员合作，继续了一项关于着色性干皮病的家族研究，以评估XP杂合子的癌症风险。数据收集工作正在进行中。神经退行性变是XP患者发病和死亡的主要原因，并因亚组而异。我们还记录了，怀孕患有三甲营养不良的孩子的母亲比怀上未受影响的孩子的母亲有更多的妊娠并发症。

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 to search for new high-risk melanoma susceptibility genes. We continue to accrue and evaluate new families in both the U.S and Italy. We have continued to evaluate families of individuals with heritable retinoblastoma and melanoma. The study of familial chordoma, a rare, low-grade, malignant bone tumor derived from remnants of the notochord, was expanded to include additional families. Recently we used array CGH to determine that duplications of the T gene (brachyury), which is important in notocord development, and is expressed in most sporadic chordomas, co-segregated with chordoma in members of four multiplex chordoma families. This was the first example of gene duplication conferring major familial susceptibility to cancer. We are currently using exome sequencing to search for disease-causing mutations in chordoma families without T gene duplications. 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 is underway. Neurologic degeneration is a major cause of morbidity and mortality among XP patients, and varies by subgroup. We have also documented that mothers carrying affected children with tricothiodystrophy have more pregnancy complications than when carrying unaffected children.