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。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。与一个国际财团合作，继续寻找其他基因。该联盟的其他研究包括确定CDKN 2A突变家族中黑色素瘤的发病率。将对高风险和低风险国家的发病率进行比较。一项国际合作研究正在进行中，以确定最常见的CDKN 2A突变Gly 101 Trp的起源。来自法国、意大利和美国的25个家庭正在进行单倍型分析，以了解Gly 101 trp突变是否来自单一祖先，如果是，突变首次出现的日期。在一项联合研究中，对48个黑色素瘤高危家族进行了候选易感基因p19 INK 4D的种系突变筛查。虽然没有发现突变，但鉴于其染色体定位在易位位点，p19 INK 4D可能是一种罕见的易感基因。对20个主要为深色肤色的意大利黑色素瘤易感家族的临床评价显示，其临床特征与在皮肤白皙人群中观察到的相似。在这些家族中，发育不良痣和黑色素瘤之间有很强的相关性。对这20个黑色素瘤易感家族的分子检测显示没有编码区CDKN 2A或CDK 4突变，这表明其他基因可能参与了这一低风险人群。回顾NF 2家族脊柱肿瘤的影像学和临床资料，发现髓内肿瘤的发病率低于神经鞘瘤和脑膜瘤。NF 2基因型影响脊柱肿瘤表型：无义或移码突变患者发生髓内肿瘤的百分比较高，并且这些和神经鞘肿瘤的平均数量高于其他类型突变的患者。家族性脊索瘤是一种罕见的、低度恶性的脊索骨肿瘤，起源于脊索的残余部分，该研究扩大到包括通过SEER系统鉴定的脊索瘤个体。一 已确定新的家庭，并正在进行评估。尝试本地化 吉恩继续说。慢性淋巴细胞白血病的研究也通过使用 新闻通讯和网站。在所研究的家庭中，似乎有证据表明存在预期。对易感基因的全基因组搜索正在进行中。其他实验室 研究包括蛋白质特性 候选基因座的表达、细胞表面标记分析、肿瘤细胞中端粒酶活性的表征和表达的免疫球蛋白重链的分析。- 基因，家族性癌症，-人类受试者和人类受试者：18岁以下的未成年人和人类受试者：仅访谈，问卷调查或调查

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. Other studies within the consortium include a determination of the penetrance of melanoma in families with CDKN2A mutations. Comparison of penetrance in high-risk and low-risk countries will be made. An international collaborative study is underway to detemine the origin of the most common CDKN2A mutation Gly101Trp. Twenty-five families from France, Italy, and the United States are being haplotyped to learn whether the Gly101trp mutation resulted from a single ancestor, and if so, the date when the mutation first appeared. In a consortium study, 48 families at high risk of melanoma were screened for germline mutations in a candidate susceptibility gene p19 INK4D. Although no mutations were found, given its chromosomal location at a translocation site, p19 INK4D may be a rare susceptibility gene. Clinical evaluation of 20 Italian melanoma-prone families with predominantly dark complexions showed that clinical features were similar to those observed in fair skinned populations. There was a strong correlation between dysplastic nevi and melanoma in these famlies. Molecular examination of these 20 melanoma-prone families revealed no coding region CDKN2A or CDK4 mutations, suggesting that other genes are likely involved in this lower risk population. Review of radiologic and clinical data on spinal tumors in memebers of NF2 families suggested that intramedullary tumors were associated with less morbidity than nerve sheath tumors or meningiomas. NF2 genotype influenced spinal tumor phenotype: a higher percentage of patients with nonsense or frameshift mutations had intramedullary tumors as well as higher mean numbers of these and nerve sheath tumors than patients with other types of mutations. The study of familial chordoma, a rare, low- grade, malignant bone tumor derived from remnants of the notochord, was expanded to include individuals with chordoma identified through the SEER system. A new family has been identified and is being evaluated. Attempts to localize the gene continue. The study of chronic lymphocytic leukemia was also expanded by use of a newsletter and a website. There appears to be evidence for anticipation among families studied. 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. - genes, familial cancer, - Human Subjects & Human Subjects: Minor under 18 Years Old & Human Subjects: Interview, Questionaires, or Surveys Only