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。与一个国际财团合作，继续寻找其他基因。我们继续积累和评估新的家庭。对意大利黑色素瘤家族的遗传分析继续进行全基因组搜索易感基因。一项试验性研究正在进行中，以评估新的意大利黑色素瘤倾向家庭的收益。 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。连锁区间并未缩小，鉴定该基因的尝试仍在继续。 对淋巴增殖性癌症家族的研究一直是人们的兴趣所在。我们描述了CLL的家系，评估的候选基因(如ATM)，潜在的易感标记(如端粒酶)，预期(家族性病例的早期发病)以及在家族背景下的关键预后因素(CD38和VH基因突变状态)。最近，我们对合适的CLL家系进行了连锁分析，确定了几个值得进一步研究的领域。我们正在对更多的家庭进行基因分型，以明确哪些领域是我们感兴趣的。我们主办了一次国际会议，以建立一个研究家族性CLL的联盟，我们将继续发展这些合作。第一项努力将是与其他主要群体合作扩大联系研究。 一项关于Waldenstrom巨球蛋白血症的新研究也已启动，目前正处于现场阶段。我们希望能尽快展开连锁性研究。非霍奇金淋巴瘤家族已经重新启动，并正在考虑发展另一个新的联盟。

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. we continue to accrue and evaluate new families. Genetic analyses of Italian melanoma families continue with a whole genome search for susceptibility loci. A pilot study is underway to assess the accrual of new Italian melanoma-prone families. The study of familial chordoma, a rare, low-grade, malignant bone tumor derived from remnants of the notochord, was expanded to include additional families. The linkage interval has not been narrowed and attempts to identify the gene continue. Studying families with lymphoproliferative cancers has been a long-standing interest. We have described CLL kindreds, evaluated candidate genes (i.e. ATM), potential susceptibility markers (i.e. telomerase), anticipation (early onset of disease in familial cases) and a key prognostic factor in the familial setting (CD38 and Vh gene mutation status). Most recently we have conducted a linkage analysis on suitable CLL kindreds which identified several areas of interest for further study. We are genotyping additional families to clarify which areas of interest to pursue. We hosted an international meeting to develop a consortium to study familial CLL adn we continue to devlop these collaborations. The first effort will be to expand the linkage study in cooperation with other major groups. A new study of Waldenstrom's macroglobulinemia was also initiated and is currently in the field phase. We hope to initiate linkage studies soon. The non-Hodgkin's lymphoma families have been reactivated, and the development of another new consortium is being contemplated.