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Genetic Epidemiology

遗传流行病学

基本信息

批准号：
10263724
负责人：
ALISA GOLDSTEIN
金额：
$ 174.77万
依托单位：
DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
依托单位国家：
美国
项目类别：
财政年份：
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/10263724
关键词：
Area BRAF gene Blood Brain Breast Cancer Genetics Breast Cancer Risk Factor Candidate Disease Gene Case-Control Studies Categories Childhood Medulloblastomas Chordoma Chronic Clinic Country Cutaneous Melanoma DNA Data Estrogens Etiology Exposure to Family Family history of General Population Genes Genetic Genetic Diseases Genetic Research Goals High-Risk Cancer Immune Individual Investigation Italy Lesion Link Malignant Neoplasms Mediating Medical Melanocortin 1 Receptor Metabolism Molecular Nervous system structure Nevus Not Hispanic or Latino Oncogenes Outcome Patients Pattern Philadelphia Population Questionnaires Receptor Gene Registries Risk Risk Factors Role Sampling San Francisco Scandinavia Site Somatic Mutation Specimen Suggestion Sun Exposure Sunscreening Agents Susceptibility Gene Testing The Sun Time Tissues Variant base cancer type carcinogenesis case control data registry disorder risk environment related cancer genetic epidemiology genome wide association study high risk malignant breast neoplasm melanoma polygenic risk score population based rate of change receptor risk variant tanning booths telomere tumor tumor DNA young woman

项目摘要

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 a case-control study of 718 non-Hispanic white patients with cutaneous melanoma from melanoma clinics in Philadelphia and San Francisco showed modest, non-significant decreased risk of melanoma among susceptible individuals who used sunscreens most of the time. Young women were the individuals most likely to use tanning beds, and use was related to melanoma risk. Those who used tanning beds were more likely to have melanomas in sites not usually exposed to sun. These observations may help explain the increasing rates and changing distribution of melanoma among young women in the general population. Questionnaire data, tumor, and DNA from a case-control study of 183 incident melanoma cases and 179 controls conducted in North-Eastern Italy, showed a strong association between germline variants in the melanocortin-1 receptor (MC1R) gene and melanoma with somatic mutations in the BRAF oncogene, in subjects with melanoma arising on sun exposed areas of the body and with limited chronic solar damage. We confirmed this association in an independent population. Data from other Mediterranean populations have been collected and harmonized to extend the analyses of association between melanoma risk and several risk factors, also including immune-related genes. In this combined sample, we identified suggestive evidence for a role of telomere-related genes in the etiology of melanoma. Moreover, a genome-wide association study (GWAS) of melanoma cases from Mediterranean countries and appropriate controls is ongoing. A polygenic risk score analysis using the GWAS data and additional data from melanoma consortia is also ongoing. Melanoma tissue specimens have been collected and analyses of melanoma lesions in relation to sun exposure, body site, nevi count, susceptibility genes and molecular alterations is planned. On

在这个遗传流行病学项目中的许多调查都来自于对癌症高危家族的观察或其他病因学研究。对费城和弗朗西斯科黑素瘤诊所718名非西班牙裔皮肤黑素瘤白色患者的病例对照研究分析显示，在大多数时间使用防晒霜的易感个体中，黑素瘤的风险适度降低，但无显著性。年轻女性是最有可能使用日光浴床的人，使用与黑色素瘤风险有关。那些使用日光浴床的人更有可能在不经常暴露在阳光下的部位患上黑色素瘤。这些观察结果可能有助于解释一般人群中年轻女性黑色素瘤发病率的增加和分布的变化。在意大利东北部对183例黑色素瘤病例和179例对照进行的病例对照研究中，问卷调查数据、肿瘤和DNA显示，黑皮质素-1受体（MC 1 R）基因的种系变异与黑色素瘤伴BRAF癌基因体细胞突变之间存在强相关性，这些受试者的黑色素瘤发生在身体暴露于阳光的区域，并伴有有限的慢性日光损伤。我们在一个独立的人群中证实了这种关联。已收集并协调了来自其他地中海人群的数据，以扩展对黑色素瘤风险与几种风险因素（包括免疫相关基因）之间关联的分析。在这个合并的样本中，我们发现了端粒相关基因在黑色素瘤病因学中的作用的提示性证据。此外，正在进行一项地中海国家黑色素瘤病例和适当对照的全基因组关联研究（GWAS）。使用GWAS数据和来自黑色素瘤财团的其他数据的多基因风险评分分析也在进行中。已收集了黑色素瘤组织标本，并计划分析与阳光照射、身体部位、痣计数、易感基因和分子改变有关的黑色素瘤病变。对