Lung cancer and tobacco use pose significant global health challenges and require a comprehensive translational roadmap for improved prevention strategies. We propose the GREAT care paradigm (Genomic Informed Care for Motivating High Risk Individuals Eligible for Evidence-based Prevention), which employs polygenic risk scores (PRSs) to stratify disease risk and personalize interventions, such as lung cancer screening and tobacco treatment. We developed PRSs using large-scale multi-ancestry genome-wide association studies and adjusted for genetic ancestry for standardized risk stratification across diverse populations. We applied our PRSs to over 340,000 individuals of diverse ethnic background and found significant odds ratios for lung cancer and difficulty quitting smoking. These findings enable the evaluation of PRS-based interventions in ongoing trials aimed at motivating health behavior changes in high-risk patients. This pioneering approach enhances primary care with genomic insights, promising improved outcomes in cancer prevention and tobacco treatment, and is currently under assessment in clinical trials.

中文翻译：

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个性化护理的基因组见解：激励高危人群采取循证健康实践

肺癌和烟草使用构成了重大的全球健康挑战，需要一个全面的转化路线图来改进预防策略。我们提出了 GREAT 护理范式（用于激励有资格进行循证预防的高风险个体的基因组知情护理），该范式采用多基因风险评分 (PRS) 来分层疾病风险并个性化干预措施，例如肺癌筛查和烟草治疗。我们利用大规模多祖先全基因组关联研究开发了 PRS，并根据遗传祖先进行调整，以实现不同人群的标准化风险分层。我们将 PRS 应用于超过 340,000 名不同种族背景的人，发现肺癌和戒烟困难的比值比显着。这些发现使得能够在正在进行的旨在促进高危患者健康行为改变的试验中评估基于 PRS 的干预措施。这种开创性的方法通过基因组见解增强了初级保健，有望改善癌症预防和烟草治疗的结果，目前正在临床试验中进行评估。