The Halifax Project: Chemical Mixtures and Cancer

描述(申请人提供)：癌症是发达国家的第二大死因。越来越多的证据表明，大多数癌症并不完全是遗传造成的，而是某种环境暴露的结果。这并不是说遗传不重要，因为每个人对化学物质或其他暴露的敏感性各不相同。环境暴露有多种，其中最重要的包括辐射和致癌化学物质。每个人都暴露在来自自然和人为来源的辐射中。我们的食物、饮用水和空气中都含有致癌化学物质。暴露发生在家里、工作场所和休闲活动中，因此每个人都暴露在致癌暴露的混合环境中。还有一些生物致癌物质，包括某些病毒、细菌和寄生虫。我们对癌症病因的大部分知识来自动物、细胞甚至人类的研究，每次只关注一种致癌物质。在现实世界中，每个人都暴露在致癌物质的混合物中。哈利法克斯项目的目标是召集来自世界各地的专家，关注环境混合物的致癌作用。将组成11个小组，每个小组处理一种特定形式的细胞级破坏。参与者将被分到专注于癌症的特定“特征”(血管生成；非调控新陈代谢；逃避抗生长信号；遗传不稳定；免疫系统逃避、复制不朽；抗凋亡；组织侵袭和转移；肿瘤微环境；肿瘤促进炎症)的小组，每个小组将确定一名首席科学家。每个小组将确定已知可选择性扰乱所分配机制的环境和/或职业化学品暴露，并考虑使用“癌症特征”框架评估破坏性环境制剂混合物对风险评估的影响。这些审查将在会议之前以草稿的形式编写。该文件将介绍该小组就其分配的主题所取得的成果和结论。一旦完成，这些综述将发表在杂志《癌症发生》的特刊上。已经达成了公布会议记录的协议。工作组的所有成员都将被列为作者。迄今为止，已有265人表示有兴趣参加，并表示希望参加11个工作组中的哪个工作组。申请者来自33个国家，其中大多数将自给自足。所需资金将用于资助国际专家，特别是来自发展中国家的专家，以及妇女、少数族裔、残疾人和其他科学家或学生的旅费，这些科学家或学生在科学界的代表性历来偏低。

DESCRIPTION (provided by applicant): Cancer is the second leading cause of death in developed countries. There is increasing evidence that most cancers are not due solely to genetics, but are rather a consequence of some environmental exposure. This is not to say that genetics are unimportant, because individuals vary in their susceptibility to chemical or other exposures. There are a variety of environmental exposures, and the most significant include radiation and carcinogenic chemicals. Everyone is exposed to radiation from natural and man-made sources. There are carcinogenic chemicals in our food, drinking water, and air. Exposure occurs at home, at the job and through leisure activities, and consequently each person is exposed to a mixture of carcinogenic exposures. There are also biological carcinogens, including certain viruses, bacteria and parasites. Much of our knowledge of causes of cancer come from animal, cellular and even human studies focused on one carcinogen at a time. In the real world, every human being is exposed to a mixture of carcinogenics. The goal of the Halifax Project is to assemble experts from around the world to focus attention on carcinogenesis of environmental mixtures. Eleven teams will be formed, each dealing with a specific form of cellular-level disruption. Participants will be placed into teams that will focus on specific "hallmarks of cancer" (angiogenesis; deregulated metabolism; evasion of anti-growth signaling; genetic instability; immune system evasion, replicative immortality; resistance to apoptosis; tissue invasion and metastasis; tumor microenvironment; tumor promoting inflammation), and a lead scientist will be identified for each team. Each team will identify environmental and/or occupational chemical exposures that are known to selectively disrupt the assigned mechanism, and consider the implications of using the "hallmarks of cancer" framework to assess the contributions of mixtures of disruptive environmental agents for risk assessment purposes. These reviews will be prepared in draft form in advance of the conference. The document will present the results and conclusions of the team on their assigned subject. Once finalized, these reviews will be published in a special issue of the journal, Carcinogenesis. An agreement to publish the conference proceedings has already been established. All members of the workgroup will be listed as authors. To date, 265 persons have expressed interest in attending and have indicated in which of the eleven workgroups they hope to participate. The applicants represent 33 countries, and most will be self-supported. Funds requested will be used for travel support for international experts, especially those from developing countries, as well as for women, racial/ethnic minorities, persons with disabilities, and other scientists or students who have been traditionally underrepresented in science.