Purpose African Americans (AAs) have the highest incidence of colorectal cancer (CRC) compared to other US populations and more proximal CRCs. The objective is to elucidate the basis of these cancer disparities. . Experimental design 566 AA and 328 Non-Hispanic White (NHW) CRCs were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability and BRAF (V600E) and KRAS mutations were tested. Statistical significance of categorical variables was tested by Fisher's exact test or logistic regression and age by Mann-Whitney U test. Results Over a ten-year period, the median age at diagnosis significantly decreased for both AAs (68 to 61; P<0.01) and NHWs (64.5 to 62; P=0.04); more AA patients were diagnosed before age 50 than NHWs (22% vs 15%; P=0.01). AAs had more proximal CRC than NHWs (49.5% vs. 33.7%; P<0.01), but overall frequencies of microsatellite instability, BRAF and KRAS mutations were not different nor were they different by location in the colon. Proximal CRCs often presented with lymphocytic infiltrate (P<0.01) and were diagnosed at older ages (P=0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant. Conclusions Patients with CRC have gotten progressively younger. The excess of CRC in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal CRCs than older ones. These data suggest two different mechanisms driving younger age and proximal location of CRCs in AAs.

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.

Colorectal cancer (CRC) affects disproportionally African Americans (AAs) who have a 20% higher incidence and a 40% higher mortality than Caucasians. Very few studies have specifically addressed CRC in AAs. In order to uncover the factors that underlie this disparity we set up the CCCC, a large, robust and well-characterized database and biorepository of CRC patients from the Chicago metropolitan area that is highly enriched with AAs. The project enrolls newly diagnosed CRCs, polyps at different stages, and cancer/polyp-free controls in 5 large hospitals. Extensive clinical, family history, demographic, dietary, toxic exposure data is collected along with tumor and uninvolved mucosa as well as plasma, serum, and paraffin-embedded samples. Tumors are molecularly characterized and germline DNA is used to assess genetic factors implicated in CRC development. The primary goal of the project is to study how genetic and environmental factors as well as their interaction contribute to CRC development and which factors make AAs more prone to develop this cancer. We will also assess specific factors that may contribute to the worse prognosis in AAs. Results: A total of 205 CRCs, (58% AAs), 86 patients with high-risk adenomas, 75 mild-risk adenomas, and 173 controls have been recruited so far. The mean age at diagnosis was 60.2 for AAs and 61.8 for whites (P=0.08), in both cases significantly lower than the mean age reported for the US CRCs in general (68-70). There was a significantly higher number of AA patients younger than age 50 at diagnosis (19.5% vs. 7.1% whites; P=0.043). In AA patients tumors were more often on the right side of the colon (43.3% vs. 22.7%; P=0.02) and more were undifferentiated (19.1% vs. 3.5%; P=0.03). Both groups had a similar number of colonoscopies before cancer diagnosis (60.2% for AAs vs. 68.3% for whites; P=0.11). While there was no significant difference among AA cases and controls regarding high tobacco use (&gt;20 pack/years)(16.9% cases vs. 17.1% controls), more whites with CRC were heavy smokers (45.7% cases vs. 29.7 controls). Less AA patients reported family history of CRC than whites (16.4% vs. 35.2%; P0.02) or family history of polyps (21.7% vs. 44%). Conclusions: In our urban cohort both AA and white patients present CRC significantly earlier than expected. Very important differences are seen between AAs and whites that may have significant implications when considering CRC screening approaches, such as the high percentage of AA patients diagnosed before age 50 or the much higher number of right-sided tumors. Heavy tobacco use seems to associate with CRC in whites but not in AAs. Altogether points towards important biological differences that need to be further assessed. As we are ascertaining toxic and dietary exposure and molecularly characterizing all tumors, eventually we should be able to explain the biological basis of the significant disparity in CRC Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3597. doi:1538-7445.AM2012-3597

<div>Abstract<p><b>Purpose:</b> African Americans (AA) have the highest incidence of colorectal cancer compared with other U.S. populations and more proximal colorectal cancers. The objective is to elucidate the basis of these cancer disparities.</p><p><b>Experimental design:</b> Of note, 566 AA and 328 non-Hispanic White (NHW) colorectal cancers were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability (MSI) and <i>BRAF</i> (V600E) and <i>KRAS</i> mutations were tested. Statistical significance of categorical variables was tested by the Fisher exact test or logistic regression and age by the Mann–Whitney <i>U</i> test.</p><p><b>Results:</b> Over a 10-year period, the median age at diagnosis significantly decreased for both AAs (68–61; <i>P</i> < 0.01) and NHWs (64.5– 62; <i>P</i> = 0.04); more AA patients were diagnosed before age 50 than NHWs (22% vs. 15%; <i>P</i> = 0.01). AAs had more proximal colorectal cancer than NHWs (49.5% vs. 33.7%; <i>P</i> < 0.01), but overall frequencies of MSI, <i>BRAF</i> and <i>KRAS</i> mutations were not different nor were they different by location in the colon. Proximal colorectal cancers often presented with lymphocytic infiltrate (<i>P</i> < 0.01) and were diagnosed at older ages (<i>P</i> = 0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant.</p><p><b>Conclusions:</b> Patients with colorectal cancer have gotten progressively younger. The excess of colorectal cancer in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal colorectal cancers than older ones. These data suggest two different mechanisms driving younger age and proximal location of colorectal cancers in AAs. <i>Clin Cancer Res; 20(18); 4962–70. ©2014 AACR</i>.</p></div>

<div>Abstract<p><b>Purpose:</b> African Americans (AA) have the highest incidence of colorectal cancer compared with other U.S. populations and more proximal colorectal cancers. The objective is to elucidate the basis of these cancer disparities.</p><p><b>Experimental design:</b> Of note, 566 AA and 328 non-Hispanic White (NHW) colorectal cancers were ascertained in five Chicago hospitals. Clinical and exposure data were collected. Microsatellite instability (MSI) and <i>BRAF</i> (V600E) and <i>KRAS</i> mutations were tested. Statistical significance of categorical variables was tested by the Fisher exact test or logistic regression and age by the Mann–Whitney <i>U</i> test.</p><p><b>Results:</b> Over a 10-year period, the median age at diagnosis significantly decreased for both AAs (68–61; <i>P</i> < 0.01) and NHWs (64.5– 62; <i>P</i> = 0.04); more AA patients were diagnosed before age 50 than NHWs (22% vs. 15%; <i>P</i> = 0.01). AAs had more proximal colorectal cancer than NHWs (49.5% vs. 33.7%; <i>P</i> < 0.01), but overall frequencies of MSI, <i>BRAF</i> and <i>KRAS</i> mutations were not different nor were they different by location in the colon. Proximal colorectal cancers often presented with lymphocytic infiltrate (<i>P</i> < 0.01) and were diagnosed at older ages (<i>P</i> = 0.02). Smoking, drinking, and obesity were less common in this group, but results were not statistically significant.</p><p><b>Conclusions:</b> Patients with colorectal cancer have gotten progressively younger. The excess of colorectal cancer in AAs predominantly consists of more proximal, microsatellite stable tumors, commonly presenting lymphocytic infiltrate and less often associated with toxic exposures or a higher BMI. Younger AAs had more distal colorectal cancers than older ones. These data suggest two different mechanisms driving younger age and proximal location of colorectal cancers in AAs. <i>Clin Cancer Res; 20(18); 4962–70. ©2014 AACR</i>.</p></div>