Abstract 2612: Personalized cancer risk and prevention: analysis of risk factors for specific cancers and integration into cancer risk assessment paradigms

R. Elespuru, Catherine G. Fischer
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Abstract

Cancer risk assessment is performed generally in relation to assessment of the safety of new medical products or environmental exposures, especially when DNA modification is a factor. The risk assessment paradigms used for products subject to regulatory review are independent of specific cancers, multiple exposures, and individual risk factors. A default cancer risk assessment for regulatory review includes “uncertainty factors” to account for differential susceptibility and other variables involved in extrapolating from experimental systems to human risk. However, there is a growing amount of evidence that suggests differing risk for different types of cancer as well as the importance of combinations of risk factors not limited to genetic or environmental effects. In the era of personalized medicine and cancer genomics, can we begin to assess personalized cancer risk, instead of overall cancer risk? What models would assist in this paradigm shift? There are several cancers for which specific genetic, environmental, viral and other associations have been established and could be used in personalized cancer risk assessments, including colon, liver, and lung cancer. A search was conducted on PubMed for available literature on epidemiology, genetic susceptibility, and risk factors associated with the major types of cancer, including ~25 pathological types of cancer in 17 different organs. Risk factors associated with each included chemical exposures and tobacco, as well as genetic, epigenetic, microbial, viral, dietary, exercise, and other factors known for involvement in the development of cancer in humans. The diversity of cancers and evidence for specific risk factors is summarized. Common risk factors, including smoking and obesity, are supplemented with a substantial set of individual, often non-overlapping risk factors for diverse cancers. Surprisingly, little evidence was found that genetic-environmental interactions are significant risk factors for most cancers. From this assessment we can begin to ask whether and for what cancers a personalized risk approach seems feasible. Disclaimer: The findings and conclusions in this presentation are those of the authors and should not be construed to represent any agency determination or policy. Citation Format: Rosalie K. Elespuru, Catherine Fischer. Personalized cancer risk and prevention: analysis of risk factors for specific cancers and integration into cancer risk assessment paradigms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2612.
2612:个性化癌症风险与预防:特定癌症的危险因素分析并整合到癌症风险评估范式中
癌症风险评估通常与评估新医疗产品的安全性或环境暴露有关,特别是当DNA修饰是一个因素时。用于接受监管审查的产品的风险评估范式独立于特定的癌症、多重暴露和个人风险因素。监管审查的默认癌症风险评估包括“不确定性因素”,以解释从实验系统推断人类风险时涉及的不同易感性和其他变量。然而,越来越多的证据表明,不同类型的癌症有不同的风险,以及不限于遗传或环境影响的风险因素组合的重要性。在个体化医疗和癌症基因组学时代,我们能否开始评估个体化癌症风险,而不是整体癌症风险?哪些模型将有助于这种范式转变?有几种癌症已经与特定的基因、环境、病毒和其他因素建立了联系,可以用于个性化的癌症风险评估,包括结肠癌、肝癌和肺癌。在PubMed上检索了与主要癌症类型相关的流行病学、遗传易感性和危险因素的现有文献,包括17个不同器官的约25种病理类型的癌症。与每种疾病相关的风险因素包括化学物质暴露和烟草,以及遗传、表观遗传、微生物、病毒、饮食、运动和其他已知与人类癌症发展有关的因素。总结了癌症的多样性和特定危险因素的证据。常见的危险因素,包括吸烟和肥胖,补充了大量不同癌症的个体,通常不重叠的危险因素。令人惊讶的是,几乎没有证据表明遗传-环境相互作用是大多数癌症的重要危险因素。根据这一评估,我们可以开始问,针对哪些癌症,个性化的风险方法是否可行。免责声明:本报告中的发现和结论是作者的观点,不应被解释为代表任何机构的决定或政策。引文格式:Rosalie K. Elespuru, Catherine Fischer。个性化癌症风险与预防:分析特定癌症的危险因素并将其纳入癌症风险评估范式[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2612。
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