Dietary and Genetic Factors in Asthma & Chronic Bronchitis in a Cohort of Chinese Singaporeans

There is suggestive evidence for a role of diet in the etiology of asthma and chronic bronchitis. However, there are few prospective data. We propose to expand our collaboration with the Singapore Chinese Health Study to examine dietary, environmental, and genetic factors, along with their interactions, in relation to the risk of developing asthma and chronic bronchitis. The Singapore Chinese Health Study (NIH grant CA080205) is a cohort of 63,257 men and women of Chinese ethnicity in Singapore who were aged 45-74 years at enrollment from 1993 to 1998. Telephone follow-up of the cohort to update and outcome information began in 1999 and is ongoing. We expect to identify 538 cases of incident asthma and 672 cases of incident chronic bronchitis when the current follow-up questionnaire cycle is complete in 2004. In this proposal, we would validate self-reports of incident asthma, obtain follow-up data from the entire cohort to perform analyses of diet and smoking in relation to these outcomes, and analyze genetic material on cases of incident asthma and chronic bronchitis and controls from the cohort. In this proposal we will examine the following hypotheses: 1. Higher intake of fruits and/or antioxidant micronutrients decreases the risk of developing asthma and chronic bronchitis. a. Effects of fruit and/or antioxidant micronutrients may differ by smoking history 2. Common polymorphisms in genes involved in the response to oxidative stress influence the risk of asthma and chronic bronchitis. We initially propose to examine polymorphisms in three genes -- glutathione S-tranferase M1, glutathione S-transferase P1, and matrix metalloproteinase-1. However, we plan to examine additional relevant polymorphisms in the future, especially taking advantage of high throughput screens of candidate genes for asthma and chronic bronchitis. It is possible that by 2004 when the sample set will be available that more compelling candidates and high throughput screens may be available to us at a low cost. Thus we will re-evaluate our choice when the samples are available. 3. Polymorphisms in these and other genes interact with fruit/antioxidant intake and/or smoking to influence the risk of asthma and chronic bronchitis.