Family Studies

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与一个国际财团合作进行。我们继续积累和评估新的家庭。意大利黑色素瘤家族的遗传分析继续进行全基因组易感位点的搜索。一项试点研究正在进行中，以评估新的意大利黑色素瘤易发家族的累积情况。

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.