Genetic And Environmental Factors In Adult Nonmalignant

该项目的目的是前瞻性地检查饮食、环境和遗传因素及其相互作用在确定新加坡超过63,000名华裔老年人患哮喘和慢性支气管炎风险方面的作用。我们扩大了由NCI资助建立的队列研究的范围，以检查饮食和癌症之间的关系，将哮喘和慢性支气管炎纳入结果。在基线登记时，队列完成了一份详细的面试者管理的饮食问卷，该问卷是专门为这一人群开发的，并在其中进行了验证。我们在关于哮喘和慢性支气管炎的后续问卷中增加了问题。我们现在正在研究基线饮食与哮喘和慢性支气管炎的关系。我们的主要假设是，更多的水果和抗氧化微量营养素的摄入可以降低患哮喘和慢性支气管炎的风险。 有证据表明，饮食在哮喘和慢性支气管炎的病因中起着重要作用。然而，几乎没有前瞻性的数据。肺内产生自由基的氧化应激似乎在哮喘和COPD的发病机制中都发挥了作用。鉴于氧化应激在哮喘和COPD发病机制中的潜在重要性，抗氧化剂可能有助于预防疾病和降低发病率。主要来自横断面数据的证据表明，摄入抗氧化性微量营养素(维生素C和E)对成人哮喘和慢性阻塞性肺疾病具有保护作用。此外，有证据表明，水果的摄入量可能是重要的，与维生素C的贡献无关，这表明水果中的其他营养物质可能是重要的。 有强有力的证据表明遗传在哮喘的病因中起到了作用，越来越多的证据表明在慢性阻塞性肺疾病中起到了作用，包括慢性支气管炎。关于吸烟的相互作用的数据很少，但最近有一些提示性的数据。目前还没有关于遗传因素和饮食之间与这些疾病相关的潜在相互作用的数据。参与炎症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基因。 这一群体特别令人感兴趣，因为据报道，新加坡和其他地方的中国女性在吸烟水平较低的情况下，慢性支气管炎的发病率很高。造成这种模式的原因尚不清楚。与西方人群相比，中国人的饮食摄入量有很大不同，西方人群一直是饮食和非恶性呼吸道疾病研究的重点。 电话跟踪问卷的管理，其中包括哮喘和慢性支气管炎的问题，已经由30,000多名受试者完成，约占队列的一半。行政管理工作将在未来两年内完成。此外，队列中还采集了血液或口腔细胞。我们已经开始初步分析基线饮食摄入量与哮喘和慢性支气管炎发病的关系。在美国胸科学会和国际环境流行病学学会的国际会议上公布的哮喘的初步结果表明，摄入水果具有保护作用。这种联系似乎在柑橘类水果和非柑橘类水果中都存在，这表明水果中除了维生素C之外的营养物质可能也很重要。我们也发现了与慢性支气管炎类似的关联。我们完成了一项建议，扩大与新加坡华人队列的合作，研究饮食、吸烟、遗传学及其与哮喘和慢性支气管炎的相互作用。该提案包括结果验证。这项提议得到了四位外部专家的好评，并获得了资助。

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.