In the USA in 2016, 134,490 cases of colorectal cancer (CRC) will be diagnosed and 49,190 people will die from this disease [1]. 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 [24]. 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.

The distribution of CRC deaths is not linear with age, with 79.1 % of deaths occurring after age 60 (Table 1) [1]. 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]. Following current trends, the incidence of colon and rectal cancer are projected to increase 124 and 90 % in subjects aged 20–34 and 27.7 and 46.0 % in subjects aged 35–49, respectively, by 2030 [5], with rectal cancer diagnosed in about two-thirds of patients <50 years [6]. While these trends are alarming, the absolute number of CRC patients in the <50 years group is still relatively small (Table 1); however, their proportion will increase relatively with continued successful screening and subsequent declines in CRC incidence among the >50 years group. 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].

Table 1 Colorectal cancer deaths stratified by age and sex, 2012.

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]. Somatic genetic and immune evaluation of African American CRCs suggests a higher proportion of KRAS mutations, a lower prevalence of microsatellite instability, a higher prevalence of elevated microsatellite alterations at selected tetranucleotide repeats, and decreased anti-tumor cytotoxic immunity than Caucasian counterparts, all of which are associated with poorer prognosis [2, 1115]. Importantly, the proportion of CRCs among African American patients aged <50 years is ~10.6 %, twice as high as Caucasians [2]. This has led some professional groups to recommend an earlier age to commence CRC screening in African Americans at age 45 in order to capture ~95 % of CRCs, as is the case with Caucasians, with some advocating screening starting as young as 40 years [2, 16].

Table 2 Incidence and death rates for colorectal cancers by race/ethnicity, 2008–2012.

With both age and race as non-modifiable drivers for CRC development, in this issue of Digestive Diseases and Sciences, Ashktorab et al. [17] set out to define the CRC incidence rates among those aged 20–44 by race to see if there was unrecognized disparity among this group similar to older CRC patients. Since their focus was on the <age 45 group, the authors specifically excluded those aged 45–49 years, among whom they presumed had undergone at least some routine screening. The authors utilized the Surveillance, Epidemiology, and End Results (SEER) data from the National Cancer Institute from 2000 to 2012, covering 27.8 % of the USA and 25.6 % of African Americans with CRC. In total, 24,520 CRC cases were diagnosed in the 12-year period, with 18,543 among Caucasians, 3581 among African Americans, and 2396 among Asian Pacific Islanders. The authors identified the highest CRC incidence among African Americans, followed by Caucasians and Asian Pacific Islanders (Table 2). They also report that the overall trends during this 12-year period are increasing for CRC in all races. Interestingly, the combined slope line for CRC incidence among Caucasians and Asian Pacific Islanders is increasing faster than the slope line for CRC incidence among African American patients. When assessing the percentage of CRCs by stage at initial diagnosis, the authors report that African Americans had the highest stage IV (18.3 %) and lowest stage II (12.1 %) among the three races, whereas Asian Pacific Islanders had the highest stage III percentage (22.0 %). Thus, increased proportions at initial diagnosis of advanced-stage CRC is also true for African Americans aged 20–44.

The data from Ashktorab et al. indicate that CRC disparities among African Americans begin at very young ages and appear to extend throughout life. This is remarkable in that adenomas are hypothesized to slowly progress over time to CRC due to prolonged exposure to the byproducts of the microbiome and user-dependent effects and thus manifest in older age; therefore, their appearance at ages 20–44 suggests the contribution of genetic factors which could be more generalizable since CRC incidence is rising for all races in this young age group. Although germline genetic evaluation for Lynch and other hereditary syndromes is strongly suggested for the younger group [7], many cases may not be due to a simple known genetic mutations but rather complex hereditary or environmental factors. Another SEER-based study among 20- to 49-year-old CRC patients demonstrated a large disparity for survival, with 5-year survival at 54.9 % for African Americans, 68.1 % for Caucasians, and 62.9 % for Hispanics [18]. Thus, there is importance to identify these young patients as early as possible to have the best chance for long-term survival.

At present, guidelines recommend CRC screening for all men and women ≥50 years, with commencement at age 40 if there is a significant family history of adenomas or CRC. This approach, with full utilization, will address the ~95 % of the population in which CRCs develop and has proven cost-effectiveness [2]. With CRC utilization rates at present in the USA at 50–60 %, further improvements in cost-effectiveness should accrue from increasing the percentage screened. [3]. To date, race is not a consideration in the Multisociety CRC Screening Guidelines, despite calls to commence CRC screening earlier for African Americans [2, 16]. It is unlikely that there will be any recommendation for universal screening among the <50 years group due to lack of cost-effectiveness with overall ~5 % prevalence of CRC for this age group (Table 1). Thus, evaluation is generally for the symptomatic patient aged <50 via diagnostic colonoscopy. Providers will need to pay attention to: (a) family history, as several in this young age group may have an identifiable hereditary syndrome via genetic testing and (b) race, as African Americans appear to have a higher incidence of CRC in both the <age 50 and >age 50 groups. Due diligence will be key for providers for anyone diagnosed with CRC prior to age 50, irrespective of race. Further investigation and study of germline and somatic genetic changes as well as very early environmental influences among this young age group might yield biomarkers to predict disease even in the absence of colonoscopic screening.