Analytical capacity building for the study of tobacco carcinogen exposures in India

摘要 世界各地与使用无烟烟草(SLT)产品相关的癌症风险差异很大。的确有 迫切需要更好地了解SLT的致癌作用，以及哪些化学成分和/或产物 这些特征决定了SLT使用者罹患癌症的风险。印度有独特的烟草负担状况 并代表了这类研究的一个迫切需要和独特的背景。近三分之一的人 印度人口正在使用各种形式的SLT，超过了吸烟的流行率。这是伴随着的 口腔和头颈部癌症(OHNC)的高发病率，这与SLT的使用密切相关，是一种 印度癌症相关死亡的主要原因。我们的建议的目标是调查 SLT产品中的致癌物含量与相关暴露以及这些产品使用者的OHNC风险之间的关系 产品，同时建设可持续烟草致癌研究计划的能力 印度。我们将重点关注烟草特有的亚硝胺N‘-亚硝胺尼古丁(NNN)和4-亚硝胺-4-亚硝胺。 (甲基亚硝基)-1-(3-吡啶)-1-丁酮(NNK)。我们的首要目标将是确定NNN的变化 和NNK在目前在孟买可获得的SLT产品中，包括广泛的制造和 我们的第二个目标将是研究NNN和NNK水平之间的关系 SLT产品以及这些产品使用者中相应生物标志物的水平。在这个目标中，我们将评估 目的1.在我们的第三个目标中，我们将比较SLT患者和SLT患者的尿NNN和NNK生物标志物水平 而且没有OHNC。总之，这些研究将对NNN和NNK的作用产生重要的见解 在印度SLT致癌方面。虽然印度公共卫生部门已经开展了大量工作 研究和倡导社区，以产生关于SLT使用、感知和 是在印度进行的。我们的研究团队处于独特的地位，可以发起这项研究，因为它将利用我们的 与塔塔纪念医院及其附属高级医院的临床医生和科学家建立合作伙伴关系 孟买癌症培训、研究和教育中心。除了产生新的科学成果之外 数据，这项研究将纳入与具体目标密切相关的能力建设活动 包括发展分析实验室能力，培训#年来自孟买的年轻调查人员 烟草研究程序、烟草产品和生物制品储存库的建立，以备将来使用 研究。

ABSTRACT Cancer risks associated with the use of smokeless tobacco (SLT) products worldwide vary drastically. There is a critical need to better understand SLT carcinogenesis, and which chemical constituents and/or product characteristics drive the risk of cancer development in SLT users. India has a unique tobacco burden profile and represents both an area of critical need and unique setting for such studies. Nearly one third of the population in India is using various forms of SLT, exceeding the prevalence of smoking. This is accompanied by high rates of oral and head and neck cancer (OHNC), which is strongly associated with SLT use and is a leading cause of cancer-related death in India. The goal of our proposal is to investigate the relationship between carcinogen content in SLT products and relevant exposures as well as OHNC risk in users of these products, while concurrently building capacity for a sustainable tobacco carcinogenesis research program in India. We will focus on the tobacco-specific nitrosamines N'-nitrosonornicotine (NNN) and 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Our first aim will be to determine the variation of NNN and NNK in SLT products currently available in Mumbai including a wide range of both manufactured and cottage-made products. Our second aim will be to examine the relationship between NNN and NNK levels in SLT products and the levels of corresponding biomarkers in users of these products. In this aim, we will assess biomarkers of exposure in 300 users of SLT products with differing NNN and NNK content, as established in Aim 1. In our third aim, we will compare levels of urinary NNN and NNK biomarkers between SLT users with and without OHNC. Together, these studies we will generate important insights into the role of NNN and NNK in SLT carcinogenesis in India. While substantial work has been carried out by the Indian public health research and advocacy community to generate valuable knowledge on SLT use, perceptions, and epidemiology, biomarker-based studies of tobacco carcinogen exposure and cancer risk have never been conducted in India. Our research team is uniquely positioned to initiate this research, as it will leverage our collaborative partnership with clinicians and scientists at Tata Memorial Hospital and its affiliated Advanced Center for Training, Research and Education in Cancer in Mumbai. In addition to generating novel scientific data, this study will incorporate capacity building activities that are closely linked to the Specific Aims and include the development of analytical laboratory capacity, training of young investigators from Mumbai in tobacco research procedures, and establishment of tobacco product and biospecimen repositories for future research.