Distribution and Determinants of Colon Cancer Risk, Survivorship and Outcomes
Fat Absorption & Colon Cancer
Fat absorption may play a critical role in colorectal carcinogenesis by determining intra-colonic exposure to carcinogens. In a large case-control study, the association between colon cancer risk and genetic variation in FABP2 and APOE was evaluated. The analysis found a negative gene x environment interaction between the FABP2 codon 54 polymorphism and fat intake in determining colorectal cancer risk. The controls from this study were used to evaluate expression of resistin-like molecules (RELM) that play a role, in animal models, in insulin resistance and intestinal inflammation. Program members demonstrated the presence of RELMβ in the plasma, with lower levels in sub-populations of non-whites, lower pack-years of cigarette smoking, and higher physical activity index levels. The direct association between RELMβ with smoking and physical activity, both of which are risk factors for colorectal cancer, suggests that RELMβ may be involved mediating the effects of these modifiable risk factors. The large case-control study also reported that the protective effects of quercetin intake, as measured by a food frequency questionnaire, were confined to proximal colon cancer and specifically when fruit intake or the Health Eating Index was high, or when tea intake was low. Conversely, for distal colon cancer, increased quercetin intake was associated with increased risk when total fruit intake is low. Smoking and diets high in red meat, both associated with colon cancer risk, may increase iron exposure, favoring colonization of certain bacterial pathogens. Program members reported an increased risk of colorectal cancer when there are exposures to both heme iron intake and pack-years, with some suggestion that antibodies against flagelin of Salmonella increased risk even further. Research for diet-microbial interactions is now planned. Program members also discovered several novel variants in Helicobacter pylori cytotoxin-associated genes and will verify these results in a bigger sample.
- Lead Researchers: Dr. Kato
- Grant: R01 CA093817
Women & Colorectal Cancer
Women Health Initiative studies lead by a program member included findings of a reduction in race-related colorectal cancer incidence between African American and white women once sociodemographic factors are considered, a reduced risk of colorectal cancer in women taking lovastatins, and a reduced risk in women taking combined hormone therapy (HR=0.72, 95% CI 0.56-0.94), however those women in the treatment group had colorectal cancers that more commonly presented with positive lymph nodes and higher stage (Simon, J Clin Oncol, 2012).
- Lead Researcher: Dr. Simon
Intervention Research with African Americans to Reduce and Eliminate Disparities
Colorectal Cancer
Although African Americans are at an increased risk of developing and dying from colorectal cancer (CRC), many efforts to encourage early detection have been unsuccessful. The long-term goal of this research is to develop cost-effective public health messages that reduce health disparities, and to examine psychological processes that serve as mechanisms explaining effective health messaging with African Americans. Program members are testing the effects of an intervention using unique versions of a CRC informational and screening video messaging system. The aims are to 1) identify and compare effects of stand-alone gain versus loss-framed health messages on African-Americans' CRC screening attitudes, intentions, and behavior; 2) identify and compare effects of gain versus loss-framed health messaging on African-Americans' perceived racism and medical mistrust; and 3) determine the effect of coupling gain and loss-framed messages with culturally-targeted personal prevention messages on African-Americans' CRC screening attitudes, intentions, and behavior.
- Lead Researcher: Dr. Lucas
Grant: R01 CA175088