The multi-racial population of Hawaii is comprised of distinct racial/ethnic groups with distinct cancer risks. Native Hawaiians experience the highest risk of developing and dying from cancer arising in the breast, lung, and stomach. By contrast, ethnic Japanese experience relatively low risks of breast and lung cancer, but are also at high risk for stomach cancer. Although such differences may be due to genetic predisposition, epidemiologic evidence points towards the diet as an important determinant of cancer risk. In particular, high consumption of fruits and vegetables, rich in antioxidant micronutrients such as the carotenoids and vitamin C, appears to be protective against breast and lung cancers. Since ethnicity is a major determinant of dietary habits, differences in the consumption of particular nutrients may account for some of the ethnic differences in cancer risk, and dietary modification within high-risk ethnic groups may prove to be an effective strategy for cancer prevention. This proposal will explore the utility of evaluating immune function in the context of cancer prevention dietary trials. Immune competence, particularly T-cell function, appears to be an important determinant of susceptibility to cancer, and dietary micronutrients including retinoids and carotenoids have been documented to influence T-cell function in vitro. These observations suggest that retinoids and/or carotenoids may influence cancer risk by virtue of their immunomodulatory effects. The proposed studies will seek evidence in support of hypotheses that dietary effects on T-cell function accounts for some of the ethnic differences in cancer risk, that T-cell function is modulated by specific dietary constituents, and that immunologic monitoring will provide intermediary endpoints for dietary trials.
The specific aims are: (1) to investigate correlations between serum micronutrient levels and T-cell function among native Hawaiians, Caucasians, and Japanese-Americans; (2) to determine whether ethnicity-related dietary constituents modulate T-cell function in vitro; (3) to determine whether dietary intervention results in detectable changes in T-cell function in vivo; (4) to design and implement a pilot cancer chemoprevention trial utilizing immunologic monitoring for intermediary endpoints.
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