Tracking 30 years of air pollution: Targeted adductomics for cancer prevention

项目摘要 众所周知，环境因素在推动全球癌症负担方面发挥着重要作用。特别是， 流行病学证据与室外空气污染的成分，如颗粒物， 和苯，增加肺癌发病率和死亡率。然而，当国际 癌症研究机构最近将室外空气污染列为已知的人类致癌物质， 承认空气污染的空间和时间变化使不同的 暴露源具有挑战性。这是确定暴露模式和设计 缓解战略。 此外，不断增加的能源消耗和人为排放直接导致空气污染。 污染这在迅速工业化的城市地区，如长江流域，尤其令人担忧 上海周边的三角洲地区，基本上所有居民都经历着不安全的空气污染水平 按日因此，解决这一问题的科学努力必须应对双重挑战： 彻底改变单一的工业和能源部门，同时提供有效的 在此期间，在个人层面上采取减轻风险的战略。 从20世纪80年代末到现在，我们进行了大量的队列和临床研究， 启东，位于长江北方岸，与上海相望。因此，我们持有大量 1989年至2018年期间从启东居民获得的样本档案，为我们提供了一个真正的 一个独特的，三十年的生物储存库，其中利用内收法来询问空气污染 暴露。 使用一种新的内收方法，在启东招募的参与者中进行了30年（1989- 2018），目标1将表征空气污染物加合物与血清白蛋白的Cys 34亲核热点。我们 假设1989年至2018年，大气污染物内照射剂量加合生物标志物将增加。 这一目标的结果将首次提供几个国家的空气污染物内部剂量数据。 几十年来，在一个经历快速工业化和肺癌风险上升的地区。 在目标2中，我们将把我们的Cys 34内收体切除术方法应用于我们之前的12周化学预防试验， 2011年在启东进行，我们证明了西兰花干预的有效性， 防止空气污染物暴露。根据我们以前的发现和初步数据，我们 假设西兰花处理将减少几种空气污染物的加合物-特别是 苯，一种已知的人类致癌物质。目标2的结果将加强现有的监测工具， 减少空气污染暴露。利用我们的生物储备库的价值，所提出的工作是独一无二的 定位，并具有重大的潜力，以推进癌症预防领域。拟议的研究 将独特地提供对三十年期间空气污染物内部剂量的客观评估 经济的快速发展和癌症风险的上升，同时也提出了经济发展的证据。 癌症二级预防战略。

Project Summary Environmental factors are known to play a major role in driving worldwide cancer burden. In particular, epidemiological evidence strongly links constituents of outdoor air pollution, such as particulate matter and benzene, to increased lung cancer incidence and mortality. Nonetheless, when the International Agency for Research on Cancer recently classified outdoor air pollution as a known human carcinogen, it acknowledged that spatial and temporal variation in air pollution makes generalization across diverse exposure sources challenging. This is a barrier to determining patterns of exposure and to designing strategies for mitigation. Moreover, increasing energy consumption and anthropogenic emissions directly contribute to airborne pollution. This is of particular concern in rapidly industrializing urban areas, such as the Yangtze River delta region surrounding Shanghai, where essentially all residents experience unsafe air pollution levels on a daily basis. Thus, scientific efforts to address this problem must meet a dual challenge: impel fundamental change to monolithic industrial and energy sectors, while simultaneously providing effective strategies for risk mitigation at the individual level in the interim. Dating from the late 1980s to the present, we have conducted numerous cohort and clinical studies in Qidong, which lies opposite Shanghai on the northern banks of the Yangtze. As a result, we hold a large archive of samples obtained from Qidong residents between 1989 and 2018, providing us with a truly unique, three-decade biorepository in which to utilize adductomic approaches to interrogate air pollution exposures. Using a novel adductomic method, in participants recruited from Qidong over three decades (1989- 2018), Aim 1 will characterize air pollutant adducts to the Cys34 nucleophilic hotspot of serum albumin. We hypothesize that adduct biomarkers of airborne pollutant internal dose will increase from 1989 to 2018. Results from this Aim will, for the first time, provide data on airborne pollutant internal dose across several decades, in a region experiencing rapid industrialization and rising lung cancer risk. In Aim 2, we will apply our Cys34 adductomics method to our previous 12-week chemoprevention trial, conducted in Qidong in 2011, in which we demonstrated the efficacy of a broccoli-based intervention in protection against airborne pollutant exposure. Based on our previous findings and preliminary data, we hypothesize that broccoli treatment will reduce adducts of several airborne pollutants – particularly benzene, a known human carcinogen. Results from Aim 2 will strengthen the tools available to monitor and mitigate air pollution exposures. Leveraging the value of our biorepository, the work proposed is uniquely positioned and has significant potential to advance the cancer prevention field. The proposed studies would uniquely provide an objective assessment of air pollutant internal dose over a three-decade period of rapid economic development and rising cancer risk, while also advancing evidence on an economical strategy for secondary cancer prevention.