Colorectal cancer is a major cause of morbidity and mortality, with more than 140,000 cases diagnosed annually in the United States. The incidence of colon cancer in New York state is 50 per 100,000 individuals, or about 4,000 cases every year. Instances of the disease are expected to increase as the national and state populations age. Despite the availability of several effective treatments, colon cancer is associated with a persistent mortality rate of about 35 percent. There is a clear need for new therapeutic strategies and effective preventive approaches for colon cancer.
Vitamin D3, or 1α,25-dihydroxycholecalciferol, has been identified as an environmental factor that impacts colon cancer risk. Higher levels of Vitamin D3, whether obtained from the diet or created within the body in response to sunlight, are correlated with reduced risk for colon cancer. Due to the importance of sunlight in generating Vitamin D3, mortality rates from colorectal cancer are higher in northeastern states such as New York than in southern states, and this difference correlates with an individual’s Vitamin D3 status. Inflammation is another factor that influences colon cancer risk. Individuals with chronic inflammatory bowel diseases such as Crohn’s disease or colitis have a 15-fold increased risk of developing colon cancer.
Although there is good evidence that high Vitamin D3 levels reduce incidence of colon cancer, little is known about how Vitamin D3 interacts with other risk factors such as inflammation. In this project, the researchers seek to understand the molecular mechanisms by which Vitamin D3 reduces risk of colon cancer, with a focus on its ability to regulate the expression of CD14, a protein that reduces tissue inflammation and modulates susceptibility to colitis. The research team will investigate how Vitamin D3, CD14, and other proteins interact to control the cross-talk between immune cells (macrophages) and tumor cells during the transition from colitis to colon cancer.