Colorectal Cancer Disparity in African Americans: Risk Factors and Carcinogenic Mechanisms

Abstract

African Americans have the highest incidence and mortality rates of colorectal cancer (CRC) of any ethnic group in the United States. Although some of these disparities can be explained by differences in access to care, cancer screening, and other socioeconomic factors, disparities remain after adjustment for these factors. Consequently, an examination of recent advances in the understanding of ethnicity-specific factors, including genetic and environmental factors relating to risk of CRC, the biology of CRC progression, and the changes in screening and mortality, is important for evaluating our progress toward eliminating the disparities. An overarching limitation in this field is the number and sample size of studies performed to characterize the etiological bases of CRC incidence and mortality in African Americans. Despite this limitation, significant differences in etiology are manifest in many studies. These differences need validation, and their impacts on disparities need more detailed investigation. Perhaps most heartening, improvements in CRC screening can be attributed to the smallest difference in CRC incidence between African Americans and whites since the late 1980s. Cancer mortality, however, remains a persistent difference.

Figure 1

A: Age-adjusted incidence rates of colorectal cancer (CRC) in African Americans (purple) and whites (green; explicitly non-Hispanic whites) from 1992 to 2014, all ages, both sexes [data from Surveillance, Epidemiology, and End Results (SEER) 13, Incidence–SEER 13 Regs Research Data, November 2016 Sub (1992 to 2014) <Katrina/Rita Population Adjustment>; https://seer.cancer.gov/data/seerstat/nov2016, accessed April 14, 2017]. Annual percentage change is depicted as text above data, where negative values indicate a decreasing trend and positive values indicate an increasing trend. Asterisks denote a rising or falling trend, where the entire 95% CI is above or below 0, respectively. No asterisk indicates a stable trend. B: Age-adjusted US mortality rates of CRC in African Americans (purple) and whites (green; explicitly non-Hispanic whites) from 1992 to 2014, all ages, both sexes (data from SEER 13). Annual percentage change is depicted as text above data, where negative values indicate a decreasing trend.

Figure 2

Cellular pathways dysregulated in colorectal cancer (CRC). Specific genetic factors that are altered in CRC and discussed in this review are blue. Figure altered from original by Wikipedia user RoadNotTaken (https://commons.wikimedia.org/wiki/File:Signal_transduction_pathways.svg, last accessed June 20, 2017). This image is being used with permission under the terms of the GNU Free Documentation License, version 1.2 or any later version, published by the Free Software Foundation (with no invariant sections, no front-cover texts, and no back-cover texts). The image herein originally appeared on November 18, 2010, and is current as of publication of this article. APC, adenomatous polyposis coli; BMP, bone morphogenetic protein; CDK, cyclin-dependent kinase; CREB, CAMP-responsive element-binding protein; EGF, epidermal growth factor; EPC, endothelial progenitor cell factors; ERK, extracellular signal–regulated kinase; FADD, Fas-associated protein with death domain; FasR, Fas receptor; GPCR, G protein–coupled receptor; GSK, glycogen synthase kinase; IGF, insulin-like growth factor; JAK, Janus-activating kinase; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase; MEKK, MAP kinase kinase kinase; MKK, mitogen-activated protein kinase kinase; PI3K, phosphatidylinositol 3-kinase; PLC, phospholipase C; RSMAD, receptor phosphorylated SMAD; RTK, receptor tyrosine kinase; SARA, SMAD anchor for receptor activation; SMO, smoothened; SOS, son of sevenless; TCF, T-cell factor; TGF, transforming growth factor; Tnf, tumor necrosis factor.