Genetic Epidemiology

遗传流行病学

• 批准号: 7064602
• 负责人: ALISA GOLDSTEIN
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7064602
• 关键词: European; Jewish; autoimmune disorder; brca gene; cancer risk; caucasian American; chronic lymphocytic leukemia; environmental exposure; family genetics; gene environment interaction; genetic susceptibility; glioma; human genetic material tag; human subject; linkage mapping; lymphoma; melanoma; multiple myeloma; neoplasm /cancer epidemiology; neoplasm /cancer genetics; ovary neoplasms; racial /ethnic difference; ultraviolet radiation

Many of the investigations in this genetic epidemiology project arise from observations in families at high risk of cancer or in other etiologic studies. A genomewide scan for linkage was conducted by the Melanoma Genetics Consortium. Examination of linkage in 49 Australian pedigrees containing at least three melanoma patients revealed evidence for linkage to chromosome 1p22. Analysis of 33 additional multiplex families from several continents plus fine mapping provided further evidence for linkage, strongest in families with the earliest mean age at diagnosis. The results provide significant evidence of a novel susceptibility gene for melanoma at 1p22. Examination of case-control study data from 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia and San Francisco and 945 matched controls from outpatient clinics with similar catchment areas to the cases revealed that for every 10% increase in average annual UVB flux, there was a 19% increase in risk of melanoma in men and a 16% increase in women. Exposure as an adult was as important as exposure as a child. People who tanned well spent much more time outdoors; among women who tanned well, for every 10% increase in hours outdoors, there was a 5.8% increase in melanoma risk. The findings imply that melanoma prevention efforts must include adult exposure and exposure among those who tan well. Analyses of the data from a population-based case-control study of ovarian cancer in Israel of the Jewish population revealed that both carriers and noncarriers of founder BRCA1/2 mutations had reduced risk of ovarian or peritoneal cancer after gynecologic surgery. The magnitude of the reduction depended upon the type and extent of surgery. 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 has been conducted. Relatives were interviewed about personal and family medical history and other risk factors and were 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 northeastern Italy identified dysplastic nevi, low propensity to tan, light eye and light skin color as the strongest risk factors for non-familial melanoma in this Mediterranean population. To investigate the genetic basis for these findings, the Asp312Asn and Lys751Gln polymorphisms of the XPD (ERCC2) DNA repair gene were analyzed. XPD variants were associated with increased risk of melanoma in older (>50 years) subjects or subjects with low-tanning ability. The 751Gln allele was associated with elevated melanoma risk among subjects without dysplastic nevi. Linked data from cancer, population, and hospital discharge registries have been 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. Analyses are ongoing to test for increased risks of LP cancers and autoimmune disorders among relatives of cases.

这个遗传流行病学项目中的许多调查来自于对癌症高危家庭的观察或其他病因学研究。 黑色素瘤遗传学联盟进行了全基因组连锁扫描。在49个澳大利亚家系中，至少有3名黑色素瘤患者的连锁检查显示与染色体1 p22连锁的证据。来自几个大陆的33个额外的多重家庭的分析加上精细的映射提供了进一步的证据，连锁，最强的家庭在最早的平均年龄诊断。这些结果为在1 p22发现一个新的黑色素瘤易感基因提供了重要证据。 来自费城和弗朗西斯科黑色素瘤诊所的718名非西班牙裔白色侵袭性皮肤黑色素瘤患者和来自门诊诊所的945名匹配对照的病例对照研究数据显示，平均年UVB通量每增加10%，男性黑色素瘤风险增加19%，女性增加16%。作为一个成年人的接触和作为一个孩子的接触一样重要。晒得好的人花更多的时间在户外;在晒得好的女性中，户外时间每增加10%，黑色素瘤风险就增加5.8%。这些发现意味着黑色素瘤的预防工作必须包括成人暴露和那些晒得很好的人暴露。 对以色列犹太人卵巢癌人群病例对照研究数据的分析显示，BRCA 1/2基因突变的携带者和非携带者在妇科手术后患卵巢癌或腹膜癌的风险降低。减少的幅度取决于手术的类型和范围。 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，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了一项以家庭为基础的研究。亲属接受了关于个人和家族病史以及其他风险因素的采访，并被要求提供口腔细胞作为DNA的来源。在关联研究和分析中，亲属将被用作神经胶质瘤病例的对照，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。 在意大利东北部进行的一项对183例偶发性黑色素瘤病例和179例对照的病例对照研究发现，发育不良痣、较低的晒黑倾向、浅色眼睛和浅色皮肤是地中海人群中非家族性黑色素瘤的最强风险因素。为了研究这些发现的遗传基础，分析了XPD（ERCC 2）DNA修复基因的Asp 312 Asn和Lys 751 Gln多态性。XPD变异与老年（>50岁）受试者或低晒黑能力受试者中黑色素瘤风险增加相关。751 Gln等位基因与无发育异常痣的受试者中黑色素瘤风险升高相关。 从丹麦和瑞典的合作者处获得了来自癌症、人群和出院登记处的关联数据，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、匹配对照以及病例和对照的一级亲属。正在进行分析，以测试病例亲属中LP癌症和自身免疫性疾病的风险增加。