Understanding the role of structural racism on racial/ethnic inequities in lung cancer risk

摘要 尽管在降低吸烟率和肺癌发病率方面取得了总体进展， 在美国，肺癌负担中持续存在的种族/民族和社会经济（SES）不平等， 重大公共卫生问题。几十年来，非裔美国人和夏威夷原住民遭受了 与其他种族/族裔群体相比，肺癌的发病率不成比例。的相关 据观察，非裔美国人和夏威夷土著人患肺癌的风险更高， 欧洲人、日本人和拉丁美洲人，在相同的一生中暴露于吸烟， 吸烟和肺癌的流行病学研究，以调查遗传因素的种族/民族差异 易感性、吸烟生物标志物和表观遗传学。虽然这些研究揭示了 分子因素与肺癌风险的种族/民族差异的关系，包括分子、遗传和个体水平 生活方式因素不能完全解释肺癌风险的种族/民族差异。因此，有一个 明确需要解决健康问题社会决定因素的上游因素，包括结构性种族主义， 影响肺癌的不平等。为了弥补这一差距，我们将利用 多种族队列研究和南方社区队列研究。这两个大群体包括超过 272，000名特征良好的成年参与者，随访时间长达27年，癌症质量高 监视数据。具体来说，我们将评估结构性种族主义和邻里撤资的影响 关于：吸烟状态和内部吸烟剂量的变化（目标1）;肺中的种族/民族和SES不平等 癌症风险（Aim 2）和血液白细胞中的DNA甲基化（Aim 3）。此外，我们将评估空气是否 污染是结构性种族主义与肺癌不平等之间关系的中介。我们亦会评估 DNA甲基化位点和表观遗传年龄是否介导了结构种族主义与肺 癌症风险（目标3）。这一建议的优点包括：1）整合了两个基于人口的群组， 在统计上有能力研究来自城市和农村的五个种族/民族群体，确保 未充分研究的高风险人群的代表性; 2）解决 结构性种族主义对吸烟和肺癌不平等的影响; 3）生物学评估 结构性种族主义体现并导致肺癌不平等的途径。时发现的问题 该提案将扩大我们对结构性种族主义对肺癌发展的贡献的理解， 结构性种族主义可能运作的潜在生物学途径。这些知识具有翻译性 为社区利益相关者、决策者和实施提供经验证据的相关性 科学家们正在研究针对吸烟和肺癌的干预措施，这也可能对健康有广泛的好处。

ABSTRACT Despite the overall progress in lowering the prevalence of cigarette smoking and incidence rates of lung cancer in the U.S., the persistent racial/ethnic and socioeconomic (SES) inequities in the burden of lung cancer are major public health problems. Over decades, African Americans and Native Hawaiians have suffered a disproportionate incidence of lung cancer in comparison to other racial/ethnic groups. The concerning observation that African Americans and Native Hawaiians experience a higher risk of lung cancer, compared to European, Japanese, and Latin Americans, for the same lifetime exposure to smoking has fueled molecular epidemiology studies of smoking and lung cancer to investigate racial/ethnic differences in genetic susceptibility, biomarkers of smoking, and epigenetics. While these studies have shed light on the contribution of molecular factors to racial/ethnic differences in lung cancer risk, both molecular, genetic and individual-level lifestyle factors are unable to account fully for the racial/ethnic differences in lung cancer risk. Thus, there is a clear need to address how upstream factors of social determinants of health, including structural racism, influence lung cancer inequities. To address this gap, we will leverage the unique epidemiological resources of the Multiethnic Cohort Study and Southern Community Cohort Study. These two large cohorts include over 272,000 well-characterized adult participants with up to 27 years of follow-up and high-quality cancer surveillance data. Specifically, we will assess the impact of structural racism and neighborhood disinvestment on: change in smoking status and internal smoking dose (Aim 1); racial/ethnic and SES inequities in lung cancer risk (Aim 2); and DNA methylation in blood leukocytes (Aim 3). In addition, we will evaluate whether air pollution mediates the relationships between structural racism and lung cancer inequities. We will also assess whether DNA methylated sites and epigenetic age mediate the association between structural racism and lung cancer risk (Aim 3). The strengths of this proposal include: 1) the integration of two population-based cohorts, statistically powered to study five racial/ethnic groups from urban and rural settings, ensuring the representation of understudied high-risk populations; 2) the public health significance of addressing the influence of structural racism on smoking and lung cancer inequities; 3) the assessment of the biological pathways by which structural racism is embodied and leads to lung cancer inequities. Findings from this proposal will expand our understanding of the contribution of structural racism to lung cancer development and the underlying biological pathways by which structural racism may operate. This knowledge has translational relevance in providing empirical evidence for community stakeholders, policy makers, and implementation scientists to develop interventions for smoking and lung cancer that also may have broad health benefits.