We are requesting continued support for an ongoing cohort study of 18,244 men, ages 45-64, living in a geographically defined area of metropolitan Shanghai, Peoples Republic of China. All cohort members have completed detailed diet and medical histories and have blood and urine samples. Questionnaires have been edited and computerized and blood and urine samples have been processed, aliquoted, and continuously stored at both -20_C and -70_C. The cohort was fully established in 1989. Follow-up of the cohort is proceeding through cancer registration by the population-based Shanghai Cancer Registry, by routine ascertainment of death certificates, and by annual recontact of all cohort members. As of March 1994, 606 have developed cancer and 989 have died. The leading cancers include lung, stomach, liver, and colorectal cancers, while stroke is the number one cause of death. Major accomplishments achieved through this cohort to date include: (1) the first direct evidence linking aflatoxin ingestion to human hepatocellular carcinoma (HCC); (2) strong evidence of synergy between aflatoxin biomarkers and chronic infection with hepatitis B virus in establishing risk of HCC; (3) failure to find an association between H. pylori serology and stomach cancer risk; (4) the absence of an inverse association between antioxidants and fatal stroke; and (5) the first comprehensive and systematic evaluations of smoking-related cancer incidence and mortality in China. We propose to continue to follow this cohort for an additional five years. We will continue to evaluate risk factors for major health outcomes in the cohort, building on previous observations and continuing to exploit the serum and urine banks available for biomarker studies. Although we did not collect buffy coats for genetic studies on cohort members, we have demonstrated that the stored serum samples contain sufficient cells for conducting selected PCR-based genetic studies. Among the scientific goals for the next five years are: (1) to continue to evaluate the aflatoxin/HCC association and to assess the impact of sequence variations in genes involved in aflatoxin metabolism (GSTM1 and EPHX) in modifying risk; (2) to continue to assess the role of H. pylori in gastric cancer etiology in Shanghai, and to assess the possible protective effect of tea polyphenols on risk; and (3) to better understand the complex interrelationships among carotenoids, smoking, and lung cancer and to assess the possible risk modifying impact of genes involved in metabolism of smoking-related carcinogens.
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