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）承担着肺癌（LC）-AA男性的高度负担 与其他种族和种族相比，从LC和LC死亡的可能性更高 知道LC差异的潜在贡献者。 定义AA吸烟者的功能，导致猜测薄荷醇烟吸烟可能部分贡献 但是，对于AAS的额外负担。 薄荷香烟吸烟在LC病因中的作用和或危害，这是由于调查表的研究， 潜在的反向因果关系，AAS，薄荷醇吸烟者和检查的代谢产物的数量不足。 此外，以前的研究并未全面探索薄荷香烟的潜在机制 吸烟和肺癌发生，突出了对研究隐藏线索的创新研究的需求 这可以解释与AAS中的薄荷卷烟有关的不良负担和差异 在流行病学证据中填补知识空白，并解决LC中薄荷香烟的实际危害 病因，我们提出了首个纳入多阶段代谢组学的基于人群的前瞻性研究 识别薄荷醇香烟吸烟相关的代谢产物及其与LC风险相关的方法 综合和成本效率的方式。 最近在南方队列研究（SCC）中生成的代谢组学数据，这是NCI资助 潜在的队列，我们​​的目标是1）使用他们 959癌症中的代谢龙的全球代谢组学平台（八个超级途径中的1,500个代谢产物） - 免费当前吸烟者（617 AA和342 EAS），并进一步评估薄荷醇的可能关联 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 LC的已知/征收风险因素（AIM 1）和2）进行嵌套的病例对照研究 每种薄荷香烟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）。 支撑研究的发现将提高我们对Menthol香烟实际危害的了解 在LC病因中吸烟，为薄荷香烟的致病/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 此外，针对种族/种族不利的人。 薄荷香烟吸烟的解释，这是导致LC负担不高的负担的潜在贡献者 在AAS中，有助于阐明隐藏的线索在LC中的种族/种族差异 LC分散研究中有关AAS吸烟悖论的知识差距。