Developing Personalized Smoking Treatment in the Southern Community Cohort Study

总结 吸烟会增加患多种癌症的风险，占所有癌症死亡人数的30%以上， 死于肺癌的人数不同社会经济和种族/民族的吸烟相关疾病负担存在差异 黑人和白人之间的癌症生存差距在20年内未能缩小。改进策略 是服务不足群体所必需的。使用生物数据个性化标准护理，以1）提高准确性 或2）测量尼古丁代谢的速度，以告知药物治疗的选择是一个 在低收入少数吸烟者中有前途但研究不足的方法。这种生物学上的个性化 治疗可以通过增加戒烟动机，提高吸烟相关健康的准确性， 风险认知，或通过其他机制。吸烟者接受基于基因的肺癌风险评估， Respiragene（由Young博士开发，顾问）更有可能接受肺癌筛查，使用尼古丁 替代疗法（NRT）和戒烟。另一个有希望的个性化干预工具是尼古丁 代谢物比率（NMR），一种反映两种尼古丁代谢物（3 '羟基可替宁/可替宁）比率的生物标志物， 非常接近CYP 2A 6基因活性。核磁共振被认为是新兴的生物标志物的选择，以衡量 尼古丁代谢，其可以被二分为“快/正常”与“慢”。来自Tyndale博士（顾问）的试验数据 表明NMR告知戒烟药物治疗的选择，使得“快速/正常”代谢者是 与“慢”代谢者相比，伐尼克兰可能戒烟。这些有希望的干预措施 在社区接受医疗保健的弱势吸烟者中进行了研究。这些初步的 在南方社区队列研究（SCCS）中，这些数据为吸烟的个性化治疗提供了一个引人注目的阶段。 我们的首要目标是利用SCCS和外展核心社区咨询委员会（CAB）， 指导两种戒烟个性化护理（PC）干预措施的开发：PC-Respiragene 和PC-NMR。PC-Respiragene和PC-NMR植根于行为变化的PRIME模型，该模型反映了 戒烟动机的多方面观点。两者都将根据低收入者的态度和信念进行调整。 社会经济地位（定义为大多数人口< 100%的联邦贫困水平） 美国东南部，烟草使用率非常高。目标1将调查居住在 田纳西州和密西西比州，以评估对吸烟相关的健康风险的看法，个性化的态度和信念 吸烟治疗，并愿意参加PC戒烟试验（n=1647）。目标2将利用CAB输入 开发PC-Respiragene和PC-NMR用于SCCS中不同的低SES社区吸烟者。目标3 将对SCCS吸烟者进行3组RCT（N=75），以试验PC-Respiragene和PC-NMR干预的可行性 并确定生物化学验证的戒烟和肺癌筛查的初步估计， 基于指南的护理（GBC）。这些目标的实现将为一个大规模的个性化随机对照试验奠定基础。 在SCCS戒烟。

SUMMARY Cigarette smoking increases the risk of multiple cancers, accounting for more than 30% of all cancer deaths and 80% of deaths from lung cancer. Disparities exist in smoking-related disease burden by socioeconomic and racial/ethnic status, and the cancer survival gap between blacks and whites has failed to close in 2 decades. Improved strategies are needed for underserved groups. Personalizing standard care with biological data to 1) enhance accuracy of lung cancer risk or 2) measure speed of nicotine metabolism to inform pharmacotherapy choice is a promising yet understudied approach in low income minority smokers. Such biologically-informed personalized treatment could benefit smokers by increasing motivation to quit, improving the accuracy of smoking-related health risk perceptions, or via other mechanisms. Smokers undergoing the gene-based lung cancer risk assessment, Respiragene (developed by Dr. Young, consultant) were more likely to undergo lung cancer screening, use nicotine replacement therapy (NRT) and quit smoking. Another promising tool for personalized intervention is the nicotine metabolite ratio (NMR), a biomarker reflecting the ratio of two nicotine metabolites (3'hydroxycotinine/cotinine) that closely approximates CYP2A6 gene activity. The NMR is considered the emerging biomarker of choice to measure nicotine metabolism, which can be dichotomized as “fast/normal” vs “slow.” Trial data from Dr. Tyndale (consultant) show that NMR informs choice of smoking cessation pharmacotherapy such that “fast/normal” metabolizers are twice as likely to quit smoking on varenicline compared to “slow” metabolizers. Neither of these promising interventions have been studied in vulnerable smokers receiving health care in the community. Taken together, these preliminary data set a compelling stage for personalized treatment of smoking in the Southern Community Cohort Study (SCCS). Our overarching aim is to leverage the SCCS and the Outreach Core Community Advisory Board (CAB) to guide the development of two personalized care (PC) interventions for smoking cessation: PC-Respiragene and PC-NMR. PC-Respiragene and PC-NMR are rooted in the PRIME Model of behavior change which reflects a multi-faceted view of motivation for tobacco cessation. Both will be tailored to attitudes and beliefs of low socioeconomic status (defined as majority of the population < 100% federal poverty level) smokers in the southeastern US, where tobacco use prevalence is very high. Aim 1 will survey SCCS smokers residing in Tennessee and Mississippi to assess attitudes and beliefs on smoking-related health risk perceptions, personalized smoking treatment, and willingness to join a smoking cessation trial of PC (n=1647). Aim 2 will leverage CAB input to develop PC-Respiragene and PC-NMR for use among diverse, low SES community smokers in the SCCS. Aim 3 will conduct a 3-arm RCT (N=75) SCCS smokers to pilot PC-Respiragene and PC-NMR interventions for feasibility and determine preliminary estimates of biochemically-validated smoking cessation and lung cancer screening at 6 months vs. guideline based care (GBC). Completion of these aims will lay groundwork for a large RCT of personalized smoking cessation in the SCCS.