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有很强的联系，例如颗粒物 和苯，以增加肺癌的发病率和死亡率。尽管如此，当国际 癌症研究机构最近将室外空气污染归类为已知的人类致癌物质 认识到空气污染的空间和时间差异使对 曝光源具有挑战性。这是确定曝光模式和设计的障碍 缓解的策略。 此外，不断增加的能源消耗和人为排放直接导致空气中 污染。这在快速工业化的城市地区尤其令人担忧，比如长江 上海周边的三角洲地区，那里几乎所有的居民都经历着不安全的空气污染水平 每天都有。因此，解决这一问题的科学努力必须迎接双重挑战：推动 从根本上改变单一的工业和能源部门，同时提供有效的 在过渡期间在个人层面上降低风险的战略。 从80年代末到现在，我们已经进行了大量的队列和临床研究 启东位于长江北岸，与上海隔江相望。因此，我们持有一大笔 1989至2018年间从启东居民那里获得的样本档案，为我们提供了一个真正的 独一无二的三十年生物信息库，其中利用内收手术方法来询问空气污染 曝光。 使用一种新的内收方法，从启东招募了30多年的参与者(- 2018)，目标1将表征血清白蛋白的Cys34亲核热点的空气污染物加合物。我们 从1989年到2018年，添加空气污染物内剂量生物标志物的假设将会增加。 这一目标的结果将第一次提供关于空气中污染物内剂量的数据 几十年来，在一个经历着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Cys34内收手术方法应用于我们之前为期12周的化学预防试验， 2011年在启东进行的，在那里我们展示了以西兰花为基础的干预在 防止暴露在空气中的污染物。根据我们之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。AIM 2的结果将加强可用于监测和 减少空气污染暴露。利用我们生物仓库的价值，拟议的工作是独一无二的 定位并具有推动癌症预防领域发展的巨大潜力。建议进行的研究 将独一无二地提供对三十年期间空气污染物内剂量的客观评估 经济的快速发展和癌症风险的上升，同时也提供了经济上 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.