Biomarkers of Lung Cancer Susceptibility in Minorities

描述（由申请人提供）：肺癌是美国癌症死亡率的主要原因。肺癌发生率和生存率的种族差异还没有得到充分的理解，可能反映了环境和遗传的影响。阐明这些因素在极高和极低风险人群中的相互作用对于制定新的干预和预防战略至关重要。这项研究的重点是非洲裔美国人谁承担了肺癌的负担不成比例和拉丁美洲人谁有非常低的利率。在我们肺癌生态遗传学研究的继续中，我们建议扩大招募非拉丁裔白人病例和对照，以比较三个种族中吸烟相关癌症风险，并测试北方加州大量非裔美国人和拉丁裔人群中首次研究的特定结果，并将探索以前从未在少数民族中研究过的基因位点。我们将收集血液或口腔标本并进行访谈，以达到三组的以下近似样本量：非拉丁裔白人（1200例，1200对照），非洲裔美国人（800例，1600对照），拉丁裔（450例，900对照）。病例将通过北方加州癌症中心（NCCC）快速病例确定计划和整个北方加州Kaiser Permanente成员进行识别。所有对照组将在年龄、种族、居住县和性别频率上进行匹配，并通过北方加州的Kaiser Permanente招募。我们将建立一个DNA库，并估计致癌物质代谢（如CYPIA 1），DNA修复（如XRCC 1）和炎症（MPO）的遗传多态性作为肺癌的危险因素的患病率。将探讨吸烟、饮食和职业风险因素的基因-环境相互作用。人口分层和遗传混合将探讨在拉丁美洲和非洲裔美国人的人口使用出生地算法和人口特异性基因标记，这些研究将有助于确定方法学解决方案，在这个多样化的人口遗传研究。以前的协会多态性性状与肺癌在高加索人不容易推广到少数民族没有进一步的详细研究，我们建议。一个特别独特的贡献，我们的研究代表了其在拉丁美洲人中唯一的广泛基础的研究，包括北方加州的15个县的集水区。这将是第二次对非裔美国人肺癌进行大型遗传流行病学研究;加州的非裔美国人一生中患肺癌的风险为11%。

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer mortality in the United States. Ethnic differences in lung cancer occurrence and survival are inadequately understood and may reflect both environmental and genetic influences. Elucidating the interplay of these factors in very high- and very low-risk populations will be crucial in developing novel intervention and prevention strategies. This study focuses on African-Americans who bear a disproportionate burden of lung cancer and Latinos who have very low rates. In this continuation of our ecogenetics study of lung cancer, we propose to expand recruitment of non-Latino Caucasian cases and controls to allow comparisons of smoking related cancer risk in three ethnic groups and test specific findings from the first study in a large population of African-Americans and Latinos in Northern California and will explore gene loci never before studied in minorities. We will collect blood or buccal specimens and interviews to achieve the following approximate sample sizes for the three groups:non-Latino whites (1200 cases, 1200 controls), African Americans (800 cases, 1600 controls), Latinos (450 cases, 900 controls). Cases will be identified through the Northern California Cancer Center (NCCC) Rapid Case Ascertainment program and through the entire Northern California Kaiser Permanente membership. All controls will be age-, race, county of residence and sex-frequency matched and recruited through Kaiser Permanente Northern California. We will establish a DNA bank and estimate the prevalence of genetic polymorphisms in carcinogen metabolism (e.g. CYPIA 1), DNA repair (e.g. XRCC1) and inflammation (MPO) as risk factors for lung cancer. Gene-environment interactions will be explored for smoking, diet and occupational risk factors. Population stratification and genetic admixture will be explored in the Latino and African American populations using both birthplace algorithms and population specific gene markers; these studies will help identify methodologic solutions to genetic studies in this diverse population. Previous associations of polymorphic traits with lung cancer among Caucasians are not readily generalizable to minorities without the further detailed study we propose. An especially unique contribution, our study represents the only broadly-based study of its kind among Latinos and includes a catchment area of 15 counties in Northern California. This will be only the second large genetic epidemiologic study of lung cancer in African-Americans; African-American men in California have an 11% lifetime risk of lung cancer.