Screening for Colorectal Cancer in African Americans: Determinants and Rationale for an Earlier Age to Commence Screening

Abstract

Colorectal cancer (CRC) screening is a highly cost-effective approach to reduce morbidity and mortality of patients, as well as reduce the prevalence of CRC in populations. Current recommendations for CRC screening for the asymptomatic general population begin at age 50 years, an age after which ~95% of cancers occur. Determinants that modify the timing and frequency for screening include a personal or family history of adenomatous polyps or CRC, the age of onset of these colonic lesions, and the presence or potential for a patient to harbor a higher-risk syndrome such as inflammatory bowel disease (IBD), familial adenomatous polyposis (FAP), or Lynch syndrome.. Although race, like family history, is a heritable factor, it has not engendered inclusion in the same broad systematic screening recommendations despite multiple studies demonstrating a disparity in the incidence and mortality from CRC, and the potential for targeted screening to reduce the disparity. In particular, African Americans, when compared to Caucasians, (a) have lower CRC screening utilization rates, (b) have an earlier presentation of CRC (0-8 years younger than Caucasians) and, more often have aggressive biological features more prone to metastasis, (c) have a higher CRC prevalence at all ages and a higher proportion of CRCs before 50 years of age (~11% vs 5% in Caucasians), (d) are less likely to know or transmit personal or family history of adenomas or CRC that might change their screening to an earlier age, (e) present with 7-15% excess right-sided CRCs that are not microsatellite unstable, (f) show higher frequencies of high-risk adenomas at every decile of age, and an excess of high-risk proximal adenomas that mirror the excess of proximal CRCs, (g) have cancers that demonstrate lower proportions of good prognostic biomarkers such as MSI and higher proportions of bad prognosticators such as EMAST, (h) may possess gut microbiota more conducive to initiating and/or propagating colonic neoplasia, and (i) may demonstrate worse outcomes with treatment for CRC. These epidemiological, biological, and genetic parameters put African Americans at higher risk from CRC irrespective of any socioeconomic issues, much like IBD, FAP, and Lynch syndrome patients. Including race as a factor to consider in national CRC screening guidelines, such as commencing screening at an earlier age than 50 years, seems rational based on the natural history and more aggressive behavior in this population.

The Increasing Incidence of Colorectal Cancers Diagnosed in Subjects Under Age 50 Among Races: CRaCking the Conundrum

“…Moreover, vigilance for a potentially inherited form of CRC must be strongly considered when a patient aged \50 years is diagnosed with this disease [7]. At present, other than heightened vigilance and evaluation of patients with a strong family history of cancer, there is no current screening strategy to address this \50 years group since it is not cost-effective as with the [age 50 years group [8].Like age, the distribution of and risk of CRC among racial and ethnic groups are not identical, with a clear disparity for African Americans for CRC incidence and death (Table 2) [1,2,9]. In conjunction with the higher incidence and death rates, African American CRC patients are initially diagnosed as many as 5-8 years earlier in age (median age of first diagnosis for African American males/ females = 66/70 years and for Caucasian males/females = 72/77 years, respectively), and have a higher prevalence of proximal precursor adenomas and CRCs as compared to Caucasians [2,10].…”

“…Indeed, age is a very powerful predictor for the development of precursor adenomas and CRC, with approximately 94.5 % of all CRCs occurring after age 50, the age at which universal CRC screening is recommended for men and women [2], although 5.5 % of all CRCs occur before age 50, when general screening is not offered or recommended unless there is a strong family history of CRC, when screening is recommended to commence at age 40 [2,3]. Over a 25-year period in a cohort of nearly 400,000 CRC patients, the incidence of CRC was reduced by 0.92 %, although this decline only occurred in subjects [age 50, and largely attributed to screening implementation [5].…”

“…In conjunction with the higher incidence and death rates, African American CRC patients are initially diagnosed as many as 5-8 years earlier in age (median age of first diagnosis for African American males/ females = 66/70 years and for Caucasian males/females = 72/77 years, respectively), and have a higher prevalence of proximal precursor adenomas and CRCs as compared to Caucasians [2,10]. Somatic genetic and immune evaluation of African American CRCs suggests a…”

“…Contributors to CRC risk for patients include age, family history, and race, as well as potentially modifiable factors such as diet, the intestinal microbiome, socioeconomic factors, physical activity, and screening utilization rates [2][3][4]. Screening, in particular, can reduce CRC mortality due to the identification and removal of precursor adenomas and potentially curable early-stage cancers; screening efficacy is manifest in the reduced CRC incidence in the USA attributed to increasing screening rates among the population [2,3]. Colonoscopic CRC surveillance likely further contributes to reduced CRC incidence and CRC-related death, particularly for patients with prior colonic neoplasms, or patients with a strong family history whether or not they have undergone any genetic evaluation for a familial syndrome.…”

“…Like age, the distribution of and risk of CRC among racial and ethnic groups are not identical, with a clear disparity for African Americans for CRC incidence and death (Table 2) [1,2,9]. In conjunction with the higher incidence and death rates, African American CRC patients are initially diagnosed as many as 5-8 years earlier in age (median age of first diagnosis for African American males/ females = 66/70 years and for Caucasian males/females = 72/77 years, respectively), and have a higher prevalence of proximal precursor adenomas and CRCs as compared to Caucasians [2,10].…”