Genetic And Environmental Factors In Adult Nonmalignant

本项目的目的是前瞻性地研究饮食、环境和遗传因素的作用，沿着它们的相互作用，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的风险中。我们扩大了一项队列研究的范围，该研究由NCI资助，旨在研究饮食与癌症之间的关系，包括哮喘和慢性支气管炎作为结果。在基线招募时，队列完成了一个详细的访谈管理的饮食问卷，专门为这一人群开发，并在此人群中验证。我们在哮喘和慢性支气管炎的随访问卷中增加了问题。我们现在正在研究基线饮食与哮喘和慢性支气管炎发展之间的关系。我们的主要假设是，多吃水果和抗氧化微量营养素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学中起作用。然而，很少有前瞻性的数据。肺中自由基产生的氧化应激似乎在哮喘和COPD的发病机制中起作用。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。主要来自横截面数据的证据表明，摄入抗氧化微量营养素（维生素C和E）对成人哮喘和慢性阻塞性肺病具有保护作用。此外，有证据表明，水果摄入量可能很重要，独立于维生素C的贡献，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，越来越多的证据表明遗传学在慢性阻塞性肺疾病（包括慢性支气管炎）中的作用。与吸烟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与这些疾病之间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者。 这一人群特别令人感兴趣，因为据报道，新加坡和其他地方的华人妇女在吸烟水平低的情况下患慢性支气管炎的比例很高。这种模式的原因尚不清楚。与西方人群相比，中国人群的饮食摄入量有很大差异，西方人群一直是饮食和非恶性呼吸道疾病研究的重点。 电话随访问卷（包含哮喘和慢性支气管炎问题）的管理已由30，000多名受试者完成，约占队列的一半。管理工作将在今后两年内完成。此外，正在收集队列中的血液或口腔细胞。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展之间的关系。在美国胸科学会和国际环境流行病学学会的国际会议上发表的哮喘的初步结果表明，水果摄入量具有保护作用。柑橘类和非柑橘类水果似乎都存在这种联系，这表明水果中含有的维生素C以外的营养物质可能很重要。我们发现慢性支气管炎也有类似的联系。我们完成了一项扩大与新加坡中国队列研究合作的建议，以研究饮食、吸烟、遗传学及其与哮喘和慢性支气管炎的相互作用。该提案包括成果验证。该提案得到了四位外部专家的积极审查，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.