Selenium, colorectal adenomas, and colon cancer.

摘要

Selenium, a trace mineral found in cereals, wheat, dairy products, meat, and fish, has received a great deal of attention as a possible cancer chemopreventive agent. The association between selenium and colorectal cancer has been studied with inconsistent results, and possible biological mechanisms have not been addressed in epidemiologic studies. This dissertation addresses several gaps in the literature on selenium and colon cancer.;Aims of this dissertation were to investigate: (1) dietary and lifestyle factors associated with serum selenium; (2) potential bias associated with the use of peri-diagnostic serum selenium due to factors such as time from symptoms to diagnosis, time from diagnosis to selenium measurement, weight change, and stage at diagnosis; (3) the association between selenium and colorectal adenomas; (4) increased apoptotic activity as a potential mechanism by which selenium acts; and (5) the association between selenium and colon cancer. Data from a large population-based case-control study of colon cancer (North Carolina Colon Cancer Study (NCCCS)) were used in conjunction with data from a cross-sectional study of colorectal adenomas (Diet and Health Study (DHS)) to evaluate these questions.;The strongest correlates of serum selenium among NCCCS population controls were age, education, alcohol use, vitamin E, and selenium supplementation. Among colon cancer cases, advanced stage at diagnosis, weight loss, and short time from diagnosis to selenium measurement were associated with lower serum selenium; these factors could contribute to bias in studies of post-diagnostic selenium and colon cancer. In our analysis of selenium and colon cancer, we found that high levels of selenium and folate jointly produced a substantially reduced risk of colon cancer. Suspected sources of misclassification (weight loss, stage at diagnosis, or time from diagnosis to blood draw) did not produce bias in our study. High selenium was also associated with a reduced prevalence of colorectal adenomas; however, our data did not suggest that apoptosis was a mechanism of action. Inconsistent results in current literature might be clarified by evaluating possible contributors to information bias (weight loss and stage at diagnosis) and investigating the interaction between selenium and folate.