Menthol cigarette smoking-related blood metabolites and lung cancer risk

薄荷醇香烟与吸烟相关的血液代谢物和肺癌风险

• 批准号: 10653537
• 负责人: QIUYIN CAI
• 金额: $ 9.86万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653537
• 关键词: Address; Adenocarcinoma; Affect; African American; African American population; Age; American; Biological; Biological Assay; Blood; Blood specimen; Cancer Etiology; Carcinogens; Cessation of life; Characteristics; Cigarette; Cohort Studies; Communities; Cotinine; Data; Diagnosis; Diagnostic; Disparity; Disparity population; Drug Metabolic Detoxication; Elasticity; Epidemiology; Ethnic Origin; Ethnic Population; Etiology; European; Funding; Future; Goals; Interdisciplinary Study; Investigation; Knowledge; Linear Models; Link; Liver Microsomes; Logistic Regressions; Low income; Malignant Neoplasms; Malignant neoplasm of lung; Menthol; Metabolic; Metabolism; Modification; Molecular; Movement; Nested Case-Control Study; Nicotine; Pathogenicity; Pathway Analysis; Pathway interactions; Plasma; Population Study; Prospective Studies; Prospective cohort; Public Health; Questionnaires; Race; Random Allocation; Reporting; Research; Risk; Risk Factors; Role; Smoker; Smoking; Socioeconomic Status; Standardization; Statistical Models; Tobacco; Validation; Variant; Woman; cancer health disparity; cancer risk; cigarette smoking; cost efficient; epidemiologic data; epidemiology study; ethnic disparity; hazard; innovation; insight; lung cancer prevention; lung carcinogenesis; male; men; metabolic profile; metabolomics; nicotine exposure; novel; population based; preventable death; racial disparity; racial population; sex; smoking-related disease

SUMMARY African Americans (AAs) bear a disproportionately high burden of lung cancer (LC)―AA males have a much higher likelihood of developing LC and dying from LC than any other race and ethnic groups. Currently, little is known about the potential contributors to the LC disparities. Menthol cigarette smoking is the most distinctive feature that defines AA smokers, leading to speculation that menthol cigarette smoking may contribute, in part, to the extra burden of LC among AAs. However, epidemiologic studies to date could not bring a full explanation of the role and/or harms of menthol cigarette smoking in LC etiology owing to questionnaire-only investigations, potential reverse causality, and insufficient numbers of AAs, menthol smokers, and examined metabolites. Moreover, previous studies did not comprehensively explore the underlying mechanisms of menthol cigarette smoking and lung carcinogenesis, highlighting the need for innovative research to investigate the hidden clues that can explain disproportional burdens and disparities related to menthol cigarette smoking among AAs. To fill the knowledge gaps in epidemiologic evidence and address the actual hazards of menthol cigarettes in LC etiology, we propose the first population-based prospective study incorporating a multi-stage metabolomics approach to identify the menthol cigarette smoking-related metabolites and their associations with LC risk in a comprehensive and cost-efficient way. Leveraging pre-diagnostic blood samples, rich epidemiologic data, and recently generated metabolomics data in the Southern Community Cohort Study (SCCS), an NCI-funded prospective cohort, we aim to 1) identify menthol cigarette smoking-related blood metabolites using the Metabolon’s Global Metabolomics platform (~1,500 metabolites in eight super pathways) among 959 cancer- free current smokers (617 AAs and 342 EAs) and further evaluate the possible associations of menthol cigarette smoking-related blood metabolites with race, sex, age, smoking intensity/duration, and other known/suggested risk factors for LC (Aim 1); and 2) conduct a nested case-control study to investigate the associations of each menthol cigarette smoking-related metabolite and a standardized metabolite risk score with LC risk, using pre-diagnostic blood samples of 80 pairs of incident LC cases (adenocarcinoma) and matched controls who were selected from cancer-free AA male current smokers within the SCCS (Aim 2). Findings from this proposed study will advance our knowledge of the actual hazards of menthol cigarette smoking in LC etiology, provide important insight into the pathogenic/molecular pathways of menthol cigarette smoking, and generate valuable information to develop new public health strategies for LC prevention mainly targeted at racially/ethnically disadvantaged people. Furthermore, this proposed study will bring a mechanistic explanation of menthol cigarette smoking, a potential contributor to a disproportionately high burden of LC among AAs, and thus help elucidate hidden clues underlying the racial/ethnic disparities in LC, which fills the knowledge gaps in LC disparities research regarding the smoking paradox among AAs.

概括 非洲裔美国人（AAS）的肺癌（LC）-AA男性的燃烧量不成比例 与其他种族和种族相比，开发LC和LC死亡的可能性更高。目前，几乎没有 知道LC分布的潜在贡献者。薄荷香烟吸烟是最独特的 定义AA吸烟者的功能，导致猜测精神病吸烟可能会在某种程度上贡献 在AAS中额外的LC燃烧。但是，迄今为止流行病学研究无法带来完整的解释 由于只有问卷调查，在LC病因中吸烟的角色和/或危害 潜在的反向因果关系，数量不足的AA，精神吸烟者和检查的代谢产物。 此外，以前的研究并未全面探索精神病香烟的基本机制 吸烟和肺癌发生，强调需要进行创新研究以调查隐藏簇 这可以解释与AAS中的薄荷香烟吸烟有关的不利伯恩斯和差异。到 在流行病学证据中填补知识空白，并解决LC中精神香烟的实际危害 病因，我们提出了第一个基于人群的前瞻性研究，编码多阶段代谢组学 识别与吸烟相关的代谢物及其与LC风险的关联的方法 全面且成本效益的方式。利用诊断前的血液样本，丰富的流行病学数据和 最近在南方社区队列研究（SCC）中生成的代谢组学数据，这是NCI资助的 潜在的队列，我们​​的目标是1）使用该薄荷香烟吸烟相关的血液代谢物使用 959癌症中的代谢龙全球代谢组学平台（八个超级途径中的1,500个代谢产物） - 免费当前吸烟者（617 AAS和342 EAS），并进一步评估Mentalhol的可能关联 与种族，性别，年龄，吸烟强度/持续时间和其他相关的吸烟相关的血液代谢物和其他 已知/建议的LC风险因素（AIM 1）； 2）进行嵌套的病例对照研究以研究 每种与吸烟相关的代谢物和标准化代谢物风险评分的关联 有LC风险，使用80对入射LC病例（腺癌）和 匹配的对照组是从无癌的AA雄性雄性吸烟者中选出的（AIM 2）。 这项拟议的研究的发现将提高我们对薄荷香烟的实际危害的了解 在LC病因中吸烟，为精神病香烟的致病性/分子途径提供重要的见解 吸烟，并生成有价值的信息，以制定新的公共卫生策略以预防LC 针对大致/种族弱势群体的人。此外，这项提出的研究将带来机械 薄荷香烟吸烟的解释，这是导致LC燃烧不成比例的潜在贡献者 在AAS中，有助于阐明LC种族/种族差异的基础的隐藏线索，这填补了 LC差异研究中有关AAS吸烟悖论的知识差距。