Genetic Epidemiology

这个遗传流行病学项目的许多调查都来自于对癌症高风险家庭的观察或其他病因学研究。对以色列犹太人卵巢癌病例对照研究数据的分析显示，BRCA1/2突变始发基因携带者和非携带者的胎次均具有保护作用。虽然口服避孕药对非携带者有保护作用，但对携带者没有保护作用。对88例儿童髓母细胞瘤的预后因素和继发恶性肿瘤进行回顾性研究。5年和10年的总生存率分别为59%和52%。在这组患者中，第二次肿瘤的风险显著增加。在一项美国皮肤黑色素瘤病例对照研究中，发现了黑色素瘤家族异质性的重要证据。很少有人有家庭成员患有胰腺癌。CDKN2A突变在这一人群中很少见。作为最近完成的DCEG成人脑肿瘤综合病例对照研究的后续研究，正在对480例符合条件的胶质瘤病例的父母、兄弟姐妹和成年子女进行一项基于家庭的研究。与亲属面谈，了解个人和家族病史及其他危险因素，并要求提供口腔细胞作为DNA来源。亲属将被用作神经胶质瘤病例关联研究和分析的对照，以评估遗传易感性和环境暴露对神经胶质瘤和病因相关肿瘤风险的作用。一项在意大利东北部进行的183例黑色素瘤病例和179例对照病例的病例对照研究确定了非家族性黑色素瘤的最强危险因素，并确定了这些因素的组合如何导致地中海人群的黑色素瘤风险。在调整了年龄、性别和色素沉着特征后，存在发育不良痣、低晒黑倾向、浅色眼睛和浅色皮肤都与黑色素瘤风险高度相关。研究人员制作了一张图表，显示了这些因素的多种组合与黑色素瘤的风险有关，以确定地中海人群中最能从预防措施中受益的患者。反匹配设计用于检测基因-环境相互作用的能力。替代措施的敏感性和特异性、遗传和环境暴露的频率以及相互作用效应的值是决定效率的最重要参数。可行性也主要取决于暴露频率和相互作用效应。虽然反匹配法仍然无法研究非常罕见的因素，但它似乎比大多数传统的流行病学方法更适合研究涉及罕见因素的相互作用。正在从丹麦和瑞典的合作者那里获得癌症、人口和出院登记的相关数据，其中包括淋巴增生性（LP）癌症病例，包括霍奇金病、非霍奇金淋巴瘤、慢性淋巴细胞白血病和多发性骨髓瘤，匹配的对照，以及病例和对照的一级亲属。在病例亲属中检查LP癌症和自身免疫性疾病风险增加的假设将被检验。

Many of the investigations in this genetic epidemiology project arise from observations in families at high risk of cancer or in other etiologic studies. Analyses of the data from a case-control study of ovarian cancer in Israel of the Jewish population revealed that parity appeared protective among both carriers and noncarriers of founder BRCA1/2 mutations. Although oral contraceptive use appeared protective among noncarriers, among carriers oral contraceptive use conferred no protection. Prognostic factors and secondary malignancies were evaluated in a retrospective study of 88 consecutive cases of childhood medulloblastoma. Overall survival was 59% at 5 years and 52% at 10 years. The risk of second neoplasms was significantly increased in this cohort of patients. Within an American case-control study of cutaneous melanoma, significant evidence for familial heterogeneity was found for melanoma. Few individuals had family members with pancreatic cancer. CDKN2A mutations were only rarely seen in this population. As a follow-up to a recently completed DCEG comprehensive case-control study of adults with brain tumors, a family-based study of the parents, siblings and adult children of the 480 eligible glioma cases is being conducted. Relatives are interviewed about personal and family medical history and other risk factors and are asked to provide buccal cells as a source of DNA. The relatives will be used as controls for the glioma cases in association studies and in analyses to evaluate the roles of genetic susceptibility and environmental exposures on the risk of gliomas and etiologically related tumors. A case-control study of 183 incident melanoma cases and 179 controls conducted in North-Eastern Italy identified the strongest risk factors for non-familial melanoma and determined how the combinations of these factors contributed to melanoma risk in Mediterranean populations. Presence of dysplastic nevi, low propensity to tan, light eye and light skin color were all highly associated with melanoma risk after adjustment for age, gender, and pigmentation characteristics. A chart showing melanoma risk associated with multiple combinations of these factors was created to identify patients who would most benefit from preventive measures in Mediterranean populations. The counter-matching design was used to examine the power for detecting gene-environment interactions. The sensitivity and specificity of the surrogate measures, the frequencies of the genetic and environmental exposures, and the value of the interaction effect were the most important parameters for determining efficiency. Feasibility was also most dependent on the exposure frequencies and interaction effect. Although still unable to study very rare factors, counter-matching appeared more appropriate than most traditional epidemiologic methods for studying interactions involving rare factors. Linked data from cancer, population, and hospital discharge registries are being obtained from collaborators in Denmark and Sweden which includes cases of lymphoproliferative (LP) cancers including Hodgkin's disease, Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, and Multiple Myeloma, matched controls, and first degree relatives of cases and controls. Hypotheses to examine increased risks of LP cancers and autoimmune disorders among relatives of cases will be tested.