Carcinogenesis is a multistep process involving the accumulation of DNA damage. Overproduction of oxidative stress, through either endogenous or exogenous sources, has been linked to oxidant-induced DNA damage. Evidence also suggests that inadequate intakes of micronutrients, such as vitamin D, may be associated with increased genomic instability. Therefore, we propose that vitamin D deficiency in conjunction with polymorphisms in oxidative stress defense and DNA damage repair genes may lead to increased cancer risks. The specific aims of the current proposal are: 1) To evaluate the chemopreventive effects of vitamin D. 2) To estimate the association of common germline genetic variations in vitamin D-regulated oxidative stress defense/DNA damage repair genes and prostate cancer (PCa) risk. Investigation of the interactions between vitamin D and genetic polymorphisms in oxidative stress defense/DNA damage repair genes will not only more precisely decipher the role of vitamin D in PCa etiology, but also add to our understanding of the molecular mechanisms in association with oxidative stress involved in PCa. Additionally, the findings of this study might provide targeted PCa prevention strategies.
