Genetic And Environmental Factors In Adult Nonmalignant

成人非恶性的遗传和环境因素

• 批准号: 6672871
• 负责人: STEPHANIE JOAN LONDON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6672871
• 关键词: Chinese; antioxidants; asthma; blood tests; chronic bronchitis; clinical research; diet; dietary constituent; dietary supplements; disease /disorder proneness /risk; gene environment interaction; genetic polymorphism; genetic susceptibility; health surveys; human subject; interview; longitudinal human study; lung disorder; passive smoking; questionnaires; respiratory disorder epidemiology; tobacco abuse; urinalysis

The aim of this project is to examine prospectively the role of diet, environmental, and genetic factors, along with their interactions, in determining the risk of developing asthma and chronic bronchitis in a cohort of over 63,000 older adults of Chinese ethnicity in Singapore. We have expanded the scope of a cohort study, established with NCI funding to examine the relation between diet and cancer, to include asthma and chronic bronchitis as outcomes. At baseline enrollment, the cohort completed a detailed interviewer administered dietary questionnaire developed specifically for, and validated in, this population. We have added questions to the follow-up questionnaire on asthma and chronic bronchitis. We are now examining associations between diet at baseline and the development of asthma and chronic bronchitis. Our primary hypotheses are that higher intake of fruits and anti-oxidant micronutrients reduce the risk of developing asthma and chronic bronchitis. There is suggestive evidence for a role of diet in the etiology of asthma and chronic bronchitis. However, there are few prospective data. Oxidative stress from production of free radicals in the lung appears to play a role in the pathogenesis of both asthma and COPD. Given the potential importance of oxidative stress in the pathogenesis of asthma and COPD, antioxidants may be useful for preventing illness and decreasing morbidity. There is evidence from primarily cross-sectional data that intakes of anti-oxidant micronutrients (vitamins C and E) are protective for asthma and chronic obstructive pulmonary disease in adults. In addition, there is evidence that fruit intake, may be important, independent of a contribution of vitamin C, suggesting that other nutrients in fruit may be important. There is strong evidence for a role of genetics in the etiology of asthma and increasing evidence for a role in chronic obstructive pulmonary disease, including chronic bronchitis. There are few data on interactions with smoking but some recent suggestive data. There are no data on potential interactions between genetic factors and diet in relation to these disorders. Genes involved in processes of inflammation and oxidative stress are candidates for interaction with dietary anti-oxidants. This population is of particular interest because the Chinese women in Singapore and elsewhere have been reported to have high rates of chronic bronchitis in the face of low levels of smoking. The reason for this pattern is unknown. This Chinese population differs dramatically in dietary intakes compared to Western populations that have been the focus of studies of diet and nonmaligant respiratory disease. Administration of the telephone follow-up questionnaire, which contains the asthma and chronic bronchitis questions, has been completed by than 30,000 subjects, about half of the cohort. Adminstration will be completed over the next two years. In addition, blood or buccal cells are being collected on the cohort. We have begun preliminary analyses of the relation between dietary intakes at baseline and the development of asthma and chronic bronchitis. Prelminary results for asthma, presented at the international conferences of the American Thoracic Society and International Society for Environmental Epidemiology show a protective effect of fruit intake. This association is seem for both citrus and noncitrus fruits suggesting that nutrients other than vitamin C contained in fruit may be important. We have found similar associations for chronic bronchitis. We completed a proposal to expand this collaboration with the Singapore Chinese Cohort to study diet, smoking, genetics and their interactions in relation to asthma and chronic bronchitis. The proposal includes outcome validation. This proposal was favorably reviewed by four outside experts and approved for funding.

该项目的目的是研究饮食，环境和遗传因素的作用，以及它们的相互作用，在确定新加坡中63,000多名中国族裔的老年人中，确定患哮喘和慢性支气管炎的风险。我们扩大了一项由NCI资金建立的队列研究范围，以检查饮食与癌症之间的关系，以包括哮喘和慢性支气管炎作为结局。在基线入学时，该队列完成了一名详细的访调员管理的饮食问卷，专门针对该人群开发并经过验证。我们在有关哮喘和慢性支气管炎的后续调查表中添加了问题。我们现在正在研究基线饮食与哮喘和慢性支气管炎的发展之间的关联。我们的主要假设是，较高的水果摄入量和抗氧化微量营养素会降低患哮喘和慢性支气管炎的风险。 有暗示性的证据表明饮食在哮喘和慢性支气管炎的病因学中作用。但是，很少有前瞻性数据。肺中自由基产生的氧化应激似乎在哮喘和COPD的发病机理中起作用。鉴于氧化应激在哮喘和COPD的发病机理中的潜在重要性，抗氧化剂可能有助于预防疾病和降低发病率。有主要来自横截面数据的证据表明，抗氧化剂微量营养素（维生素C和E）的摄入量是针对成人哮喘和慢性阻塞性肺部疾病的保护性。此外，有证据表明，果实摄入可能很重要，与维生素C的贡献无关，这表明水果中的其他营养素可能很重要。 有强有力的证据表明遗传学在哮喘病因学中的作用以及越来越多的证据表明在慢性阻塞性肺部疾病中发挥作用，包括慢性支气管炎。关于吸烟的相互作用的数据很少，但最近有一些暗示性数据。与这些疾病有关的遗传因素与饮食之间的潜在相互作用没有数据。涉及炎症过程和氧化应激过程的基因是与饮食抗氧化剂相互作用的候选物。 该人群特别令人感兴趣，因为据报道，新加坡和其他地方的中国妇女面对吸烟水平低的慢性支气管炎率很高。这种模式的原因未知。与西方人群相比，饮食摄入量与饮食研究的重点和非症状呼吸道疾病的重点相比，这种中国人口在饮食摄入量方面有很大差异。 电话后续调查问卷包含哮喘和慢性支气管炎问题，已完成了30,000多名受试者，约占队列的一半。接下来的两年将完成管理。另外，在队列上收集了血液或颊细胞。我们已经开始对基线饮食摄入量与哮喘和慢性支气管炎的发展之间的关系进行初步分析。哮喘的初步结果，在美国胸部学会和国际环境流行病学学会的国际会议上提出，表明了水果摄入的保护作用。这种关联似乎是柑橘类和非柑橘类水果，表明水果中含有维生素C以外的其他营养可能很重要。我们发现了类似的慢性支气管炎的关联。我们完成了一项提议，以扩大与新加坡中国队列的合作，以研究饮食，吸烟，遗传学及其相对于哮喘和慢性支气管炎的相互作用。该提案包括结果验证。该提案经过四位外部专家的审查，并批准了资金。