Neoplasm Epidemiology: 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。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。有V126D突变（CDKN2A的一种常见突变）的七个北美家庭的halotype与一个共同的创始人一致。这种突变似乎出现在34-52代以前，但它出现的位置尚不清楚。在20个美国黑色素瘤易发家族中，研究了发育不良痣和黑色素瘤之间的基因协变量相互作用，其中13个家族有CDKN2A突变。发育不良痣、全痣或两者都是重要的协变量，但日晒不是。在没有CDKN2A突变的家庭中，发育不良痣的影响更大。家族性脊索瘤是一种罕见的、低级别的、源自脊索残余的恶性骨肿瘤，其研究扩大到包括两个新的家族。基于这些家族，受影响的多点分析仅显示标记D7S500的最大LOD评分为4.78，从标记D7S512到标记D7S684的支持间隔为2 LOD。鉴定该基因的努力仍在继续。慢性淋巴细胞白血病的研究也通过通讯和网站得到了扩展。对易感基因的全基因组搜索正在进行中。其他实验室研究包括候选基因座的蛋白表达表征、细胞表面标记分析、肿瘤细胞端粒酶活性表征以及表达的免疫球蛋白重链分析。一项针对华登斯特罗姆氏巨球蛋白血症的新研究也已启动，目前处于实地研究阶段。

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). 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. Seven North American families with the V126D mutation, a common mutation of CDKN2A, had halotypes consistent with a common founder. The mutation appears to have arisen 34-52 generations ago, but the location where it arose is unknown. The gene covariate interaction between dysplastic nevi and melanoma was explored in 20 American melanoma-prone families, 13 of which had CDKN2A mutations. Dysplastic nevi, total nevi, or both were important covariates, but sun exposure was not. The effect of dysplastic nevi appeared greater in families without CDKN2A mutations. The study of familial chordoma, a rare, low-grade, malignant bone tumor derived from remnants of the notochord, was expanded to include two new families. Based on these families, multipoint analyses of affecteds only revealed a maximum LOD score of 4.78 at marker D7S500, with a 2-LOD support interval from marker D7S512 to marker D7S684. Attempts to identify the gene continue. The study of chronic lymphocytic leukemia was also expanded by use of a newsletter and a website. A genome-wide search for susceptibility genes is in progress. Other laboratory investigations include characterization of protein expression of candidate loci, cell surface marker analysis, characterization of telomerase activity in tumor cells, and analysis of expressed immunoglobulin heavy chains. A new study of Waldenstrom's macroglobulinemia was also initiated and is currently in the field phase.