Background: Colorectal cancer (CRC) is the third leading cause of cancer-related death in both sexes in the United States. While the overall CRC incidence rates have declined over the past 10 years, the disparity between African Americans (AAs) and non-Hispanic whites has increased and the incidence in AAs remains higher than in other populations. Very few studies have specifically addressed CRC in AAs, and important studies on CRC almost never include significant numbers of AAs to draw any firm conclusions.
Objective: To establish a large, robust and well-characterized database and bio-repository collection of CRC from AA patients and controls strengthening a collaborative working group, the Chicago Colorectal Cancer Consortium (CCCC), which spans 5 of the main hospitals of the Chicago area. We collect clinical, demographic and dietary data; and a biological repository of specimens consisting of tumor and non-tumor genomic DNA, RNA, plasma, serum, and paraffin-embedded samples.
Specific Aims: The primary goal of the project is to study how genetic and environmental factors and their interaction result in the development of CRC. We will also study prognosis determinants in the AA population.
Results: Recruitment and data collection: So far we have recruited 56 AA and 17 white-non Hispanic adenocarcinoma colorectal patients. We have also recruited 84 AAs and 32 white patients with adenomatous polyps, and 44 AAs and 30 white controls (individuals without polyps or previous history of polyps). From all individuals we have collected demographic/socioeconomic data, clinical data, family history of cancer, medication and toxic substance history, and dietary data using the Block Brief 2000 Food Frequency Questionnaire.
Preliminary analyses: To identify potential variables that could influence the cancer disparity between AAs and whites, we performed a preliminary analysis of all these data using a Fisher exact test.
A systematic molecular analysis of BRAF and KRAS mutations, microsatellite instability and presence of CpG island methylation phenotype in all CRC tumors is being performed. We are also analyzing protein expression of the mismatch repair genes through immunohistochemistry. We will test for an association between these molecular features and clinical variables. Moreover, 1 year follow-up data is already available and being collected on 23 cases. Therefore, we will soon be able to start investigating the relationship of those molecular features with survival and specific chemotherapy response. Summary: The preliminary analysis has highlighted some significant differences between AA and white CRC patients. In comparison with white patients, a higher proportion of AA patients are less than 50 years at diagnosis, take NSAIDS, and fulfill Bethesda criteria, which is a set of criteria to select out patients to be pre-screened for mismatch repair deficiency and eventually for genetic testing to rule out Lynch syndrome.
It has also highlighted that CRC patients have a lower level of education than cancer-free individuals in both ethnicities. This type of sociocultural disparities could potentially be associated with different life styles. In fact, AA CRC cases consumed more carbohydrates than controls reflecting this potential life style difference.
Cancer Relevance: Understanding the key molecular features and environmental factors that impact CRC development in the AA population is of paramount importance given the scarce information available. Understanding the role genetic factors will be crucial to help risk stratify patients, recommend screening modalities, and recommend preventive measures. When this information is combined with environmental factors, such as dietary habits, we will be able to offer a comprehensive personalized medicine approach for AA CRC patients.
Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B73.
