Biomarkers of Lung Cancer Susceptibility in Minorities

描述(申请人提供)：肺癌是美国癌症死亡的主要原因。人们对肺癌发生和存活的种族差异了解不足，可能反映了环境和遗传因素的影响。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。这项研究的重点是肺癌负担不成比例的非洲裔美国人和发病率非常低的拉美裔美国人。在我们对肺癌的生态遗传学研究的继续中，我们建议扩大非拉丁裔高加索病例和对照的招募，以比较三个种族中与吸烟相关的癌症风险，并在北加州的大量非裔美国人和拉丁裔人群中测试第一项研究的具体结果，并将探索在少数族裔中从未研究过的基因位点。我们将收集血液或口腔样本并进行访谈，以获得以下三组人群的大致样本量：非拉丁裔白人(1200例，1200名对照)，非裔美国人(800例，1600名对照)，拉丁裔(450例，900名对照)。病例将通过北加州癌症中心(NCCC)快速病例确定计划和整个北加州凯撒永久会员资格进行识别。所有的控制者都将通过北加州凯撒永久医院进行年龄、种族、居住地和性别频率的匹配和招募。我们将建立一个DNA文库，评估致癌物质代谢(如CYPIA 1)、DNA修复(如XRCC1)和炎症(MPO)等基因多态是否为肺癌的危险因素。将探索吸烟、饮食和职业风险因素的基因-环境相互作用。将使用出生地算法和特定于群体的基因标记在拉美裔和非裔美国人群体中探索群体分层和遗传混合；这些研究将有助于确定在这一多样化群体中进行遗传研究的方法论解决方案。如果没有进一步的详细研究，以前高加索人肺癌与多态特征的关联很难推广到少数族裔。一项特别独特的贡献是，我们的研究代表了唯一一项在拉美裔中进行的此类广泛研究，包括加利福尼亚州北部15个县的集水区。这将只是第二项关于非裔美国人肺癌的大型遗传流行病学研究；加利福尼亚州的非裔美国人男性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.