Incidence Of Early-onset Colorectal Cancer Research Articles

Detailed incidence and mortality trends of early-onset colorectal cancer in Canada.

e15539 Background: There has been a consistent increase in the incidence of early-onset colorectal cancer (eoCRC), under the age of 50, in Canada since the late 1990s. Questions remain surrounding how these trends vary by topography, histology, and stage, and related trends with CRC-specific mortality. Methods: CRC incidence data were obtained from the Canadian Cancer Registry and CRC-specific mortality data from the Canadian Vital Statistics – Death Database for the years 2000 to 2017. Age-specific average annual percent changes (AAPC) in the incidence (by topography and histology) and mortality rates of CRC were estimated using the National Cancer Institute’s Joinpoint Regression Program. To determine age-specific differences (5-year age groups) in CRC diagnosis at late stage (III and IV) for years 2011 to 2017 combined, a logistic regression model adjusting for sex with the 50-54 age group as the referent was conducted. Results: AAPCs and 95% confidence intervals in the rates of incidence (topography and histology) and mortality of eoCRC from 2000 to 2017 in Canada are presented in Table. Different trends in topography were observed across sexes with the largest increases in the distal colon (splenic flexure, descending, and sigmoid) and rectum among males and rectum only among females. Significant increases were observed for non-mucinous adenocarcinomas, while significant decreases were observed for mucinous adenocarcinomas among the 40-49 age group. Compared to the 50-54 age group, only the 45-49 group had a significantly higher odds of developing late-stage colon cancer, while men and adults 25-49 had a higher odds of developing late stage rectal cancer. Despite increases in the incidence of eoCRC there has only been a significant increase in mortality for men aged 20-39. Trends in mortality vary by site, with significant decreases observed for colon cancer-specific mortality among the 40-49 age group and increases in rectal cancer-specific mortality for adults aged 20-49. Conclusions: These results indicate that the largest increases in incidence and mortality for eoCRC have occurred in the rectum and trends have varied by sex. Further research on the etiology and treatment outcomes of eoCRC patients are warranted for this patient population.[Table: see text]

Early-onset stage II/III colorectal adenocarcinoma in the IDEA database: Treatment adherence, toxicities, and outcomes from adjuvant fluoropyrimidine and oxaliplatin.

3517 Background: Incidence of early-onset colorectal cancer (eoCRC, age < 50) is steadily increasing. Decisions on adjuvant treatment (adjTx) regimen and duration should consider tx adherence, toxicity (tox) and expected outcomes in a population with life-expectancy longer than late onset CRC (loCRC, age ≥ 50). Methods: Individual patient data from stage II/III patients (pts) from 6 randomised trials in the IDEA database were used to compare characteristics, tx adherence, and adverse events of eoCRC to loCRC. To reduce the confounder of non-cancer-related deaths due to age/co-morbidities, time-to-recurrence (TTR) and cancer-specific survival (CSS) were compared by stratified Gay k-sample test. 5-year cancer-specific mortality (CSM) rate were estimated by adjusted cumulative incidence function. 3-year relapse-free survival (RFS) rate were compared by stratified and adjusted COX models. Results: Out of 16,349 pts included, 1564 (9.6%) were eoCRC. Compared to loCRC, eoCRC had lower percent of male pts (51% vs 57%, p < 0.01) better performance status (PS0 86% vs 80%, p < 0.01), similar T stage distribution (% T1-3/T4: 76/24 vs 77/23, p = 0.97), higher rate of N2 disease (24% vs 22%, p < 0.01), more likely to complete pre-planned duration of adjTx (83.2% vs 78.2%, p < 0.01) and received a higher tx intensity especially with 6 month tx (mean oxaliplatin dose intensity 75% vs 72%, p < 0.01; capecitabine 85% vs 78%, p < 0.01; 5FU 85% vs 82% p < 0.01). Gastrointestinal tox was more common in eoCRC (any grade nausea 58% vs 45%, p < 0.01; any grade vomiting 22% vs 16%, p < 0.01); haematological tox was more frequent in loCRC (62% vs, 69%, p = < 0.01); any grade neuropathy rate was similar (75%). Significant interaction was found between age and T stage for TTR (p = 0.04). Clinical outcome estimates and comparisons are shown in Table. Notably, high risk stage III (T4/N2) eoCRC had significantly lower 3-y RFS rate (54% vs 64%, HRadj 0.74, p < 0.01). Conclusions: eoCRC have better tx adherence than loCRC, as expected. While in high risk stage II and low risk stage III, cancer-specific outcomes are not different, in high risk stage III young age is negatively prognostic and associated with significantly higher relapse rate and risk of CRC death; this is despite a higher administered adjTx-intensity, suggesting a more aggressive disease biology. Clinical trial information: NCT00749450 (SCOT); NCT00646607 (TOSCA); NCT01150045 (CALGB/SWOG 80702); NCT00958737 (IDEA France) [Table: see text]

Effect of Medicaid expansion on incidence of early-onset colorectal cancer incidence among Hispanics.

3547 Background: Early onset colorectal cancer (EO-CRC, age < 50 years) is an emerging public health crisis; especially in Hispanics. Access to healthcare is critical for timely detection and is tied to medical insurance. In 2010, the Affordable Care Act allowed for expansion of Medicaid eligibility across the country, however, states were permitted to opt out by the US Supreme Court ruling of 2012, which created an unintended experiment in the healthcare market. We evaluated the effects of Medicaid expansion on the incidence of EO-CRC among Hispanics with the hypothesis that it would lead to an increase in incidence and early detection EO-CRC. Methods: The National Cancer Data Base was used to collect data on newly diagnosed Hispanics with EO-CRC (40-49 years), across all stages, from 2010-2017. Data for 21 expansion states (ES) that expanded Medicaid in 2014, and 16 non expansion (NES) states was analyzed. The yearly state-wise Hispanic population was collected from U.S Census Bureau for 2010-17. Incidence was computed as number of new cases of CRC divided by size of the state’s Hispanic population. Segmented Poisson generalized linear mixed effects model was used to analyze rate of change in yearly incidence of EOCRC before and after 2014, in ES and NES. Results: Average annual incidence (AI) of EO-CRC in Hispanics was 6/100,000 and 8/100,000 pre and post expansion, in ES, and 8/100,000 and 9/100,000 pre and post 2014 in the NES, respectively. Increase in AI of EO-CRC was 3.6% per year (2010-14) (95% CI: -0.1% to 7.4%), and 9.8% (2014-17) (95% CI: 5.2% to 14.7%) for ES states; and 6.4% (2010-14) (95% CI: 2.1% to 10.8%), and 1% (2014-17) (95% CI: -3.8% to 6.1%) in NES. ES showed greater change in EO-CRC incidence post expansion (2014) vs. pre-expansion, as compared to NES (p=0.078) table. There was no difference in stage at diagnosis between pre- and pos- expansion periods between ES and NES. Conclusions: Increase in incidence of EO-CRC in ES is likely due to greater access to health care due to Medicaid coverage as compared to NES. Other potential factor is migration of Medicaid eligible persons from NES to ES. However we need data past 2017 to confirm the current trend.[Table: see text]

Gut instinct: a call to study the biology of early-onset colorectal cancer disparities.

Colorectal cancer (CRC) incidence among individuals age younger than 50 years continues to rise with etiologies unknown. Synchronously, early-onset CRC disparities have grown more pronounced. As translational research across diverse populations has been limited, we advocate for mechanistic studies that address this challenge to mitigate CRC disparities among young adults. The incidence of early-onset colorectal cancer (EOCRC) continues to rise and disproportionately affects people of African descent. This Comment advocates for mechanistic studies that can help mitigate EOCRC disparities.

Patients with Early-Onset Colorectal Cancer Have an Increased Risk of Second Primary Malignancy.

While overall colorectal cancer (CRC) rates in the USA are declining, the incidence of early-onset CRC (eoCRC) under age 50 is increasing. The aim of this study was to examine the risk of a second primary malignancy (SPM) in individuals with eoCRC, and how this risk compares to those with late-onset CRC (loCRC). We used data from the Surveillance, Epidemiology, and End Results Program database to examine the risk of SPM after a diagnosis of eoCRC. Standardized incidence ratios (SIR) were used to estimate the risk of SPM after eoCRC and loCRC in comparison with the risk of malignancy in the general population. Compared to the general population, individuals with eoCRC, but not loCRC, had an increased lifetime risk of SPM (SIR 1.42, 95% CI 1.37-1.48 and SIR 1.00, 95% CI 0.99-1.02, respectively), and locations at highest risk were the small intestine, ureter, rectum, and colon. The risk of SPM after eoCRC was similar in men and women, but higher in non-whites compared to whites and higher in those with a lower area-level median household income. The risk of SPM following eoCRC was high in the first 5years after diagnosis (SIR 2.44, 95% CI 2.24-2.66) and, in a birth cohort analysis, was found to be increasing over time. Individuals with eoCRC have a lifetime risk of SPM nearly 50% higher than the general population. The risk of SPM is highest in the first 5years after diagnosis and is increasing over time.

The impact of primary tumor sidedness on survival in early-onset colorectal cancer by stage: A National Veterans Affairs retrospective analysis.

BackgroundThe incidence of early‐onset colorectal cancer (EOCRC) is rising. Left‐sided colorectal cancer (LCC) is associated with better survival compared to right‐sided colon cancer (RCC) in metastatic disease. NCCN guidelines recommend the addition of EGFR inhibitors to KRAS/NRAS WT metastatic CRC originating from the left only. Whether laterality impacts survival in locoregional disease and EOCRC is of interest.Methods65,940 CRC cases from the National VA Cancer Cube Registry (2001–2015) were studied. EOCRC (2096 cases) was defined as CRC diagnosed at <50 years. Using ICD codes, RCC was defined from the cecum to the hepatic flexure (C18.0–C18.3), and LCC from the splenic flexure to the rectum (C18.5–18.7; C19 and C20).ResultsEOCRC is more likely to originate from the left side (66.65% LCC in EOCRC vs. 58.77% in CRC). Overall, LCC has better 5‐year Overall Survival (OS) than RCC in stages I (61.67% vs. 58.01%) and III (46.1% vs. 42.1%) and better 1‐year OS in stage IV (57.79% vs. 49.49%). Stage II RCC has better 5‐year OS than LCC (53.39% vs. 49.28%). In EOCRC, there is no statistically significant difference between LCC and RCC in stages I‐III. Stage IV EOCRC patients with LCC and RCC have a 1‐year OS of 73.23% and 59.84%, respectively.ConclusionIn EOCRC, LCC is associated with better OS than RCC only stage IV. In the overall population, LCC is associated with better OS in all stages except stage II. The better prognosis of stage II RCC might be due to the high incidence of mismatch repair deficient tumors in this subpopulation.

The Inherited and Familial Component of Early-Onset Colorectal Cancer.

Early-onset colorectal cancer (EOCRC), defined as that diagnosed before the age of 50, accounts for 10–12% of all new colorectal cancer (CRC) diagnoses. Epidemiological data indicate that EOCRC incidence is increasing, despite the observed heterogeneity among countries. Although the cause for such increase remains obscure, ≈13% (range: 9–26%) of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% of patients with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. Approximately 28% of EOCRC patients have family history of the disease. This article recapitulates current evidence on the inherited syndromes that predispose to EOCRC and its familial component. The evidence gathered support that all patients diagnosed with an EOCRC should be referred to a specialized genetic counseling service and offered somatic and germline pancancer multigene panel testing. The identification of a germline pathogenic variant in a known hereditary cancer gene has relevant implications for the clinical management of the patient and his/her relatives, and it may guide surgical and therapeutic decisions. The relative high prevalence of hereditary cancer syndromes and familial component among EOCRC patients supports further research that helps understand the genetic background, either monogenic or polygenic, behind this increasingly common disease.

High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer

The global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.

Positive Fecal Immunochemical Test Strongly Predicts Adenomas in Younger Adults With Fatty Liver and Metabolic Syndrome.

INTRODUCTION:The incidence of early-onset colorectal cancer is increasing. This study explored the feasibility of fecal immunochemical test (FIT) and risk factors for predicting colorectal neoplasm in younger adults.METHODS:This single-center study included 6,457 participants who underwent health examination from 2013 to 2016 including index colonoscopy (3,307 individuals aged 30–49 years as the younger adult group and 3,150 aged ≥50 years as the average-risk group). Primary outcomes were adenoma detection rate (ADR) and advanced ADR (AADR). Findings of younger participants were stratified by the results of FIT and clinical risk factors and were compared with those of the average-risk group.RESULTS:Among participants aged 30–49 years, a positive FIT was associated with significantly higher ADR (28.5% vs 15.5, P < 0.001) and AADR (14.5% vs 3.7%, P < 0.001) than a negative FIT. Moreover, a positive FIT was associated with higher AADR in younger participants than in average-risk counterparts (14.5% vs 9.8%, P = 0.028). Although no single risk factor predicted FIT positivity in younger participants, nonalcoholic fatty liver disease was independently associated with higher ADR (odds ratio = 2.60, 95% confidence interval = 1.27–5.34, P = 0.001), and metabolic syndrome was independently predictive of higher AADR in younger participants than in average-risk participants (odds ratio = 3.46, 95% confidence interval = 1.66–7.21, P = 0.001).DISCUSSION:A positive FIT in people aged 30–49 years implies a higher risk of colorectal neoplasm, particularly among patients with nonalcoholic fatty liver disease and metabolic syndrome.

Racial ethnic disparities in clinical/pathological features, treatment, and survival among patients with early-onset colorectal cancer.

21 Background: Globally, the incidence of early-onset colorectal cancer has risen. Racial disparities in colorectal cancer (CRC) are well-described, however data in EO by race/ethnicity is lacking. We aim to compare the presenting features, treatment, and survival features of patients with metastatic early-onset CRC (EO). Methods: Patients with metastatic CRC diagnosed between 2010-2019 at two NYC hospitals were identified by tumor registry (n = 646). Clinical/pathological features, treatment and survival data was collected by chart review and compared between Non-Hispanic Whites (NHW), Non-Hispanic Blacks (NHB) and Hispanics (H) using Chi-square or Fisher’s exact test. Kaplan Meier curves were plotted to compare overall survival (OS) among groups. Stata v15 was used for statistical analysis. Results: Of 646 CRC patients, 126 (21.5%) were NHW, NHB or H diagnosed with EO with a frequency ranging from 16.6% in NHW to 26.1% in H. Non statistically significant lower frequencies of male gender, low/moderate grade, left-sided tumors,and higher frequency of KRAS mutations were seen in NHB (Table). Metastectomy was performed in 20 patients (13.9%) and did not differ between groups. There was no difference in the use of chemotherapy or biologics in general (Table), but NHW were more likely to get cetuximab than NHB (OR:4.5, p = 0.02) and H (OR:4.7, p = 0.02).There were no differences in median OS (1.8 vs. 2.2 vs. 2 years, p = 0.9)or 1-year OS (72% vs 72.3% vs 70.8%) in NHW, NHB and H, respectively. A lower 5-year OS was seen in NBH (14.5%) and Hispanics (24.4%) compared to NHW (44%). Conclusions: EO-CRC is more frequently seen in minority racial/ethnic groups. Despite no differences in the use of chemotherapy or biologic treatment in general, NHB have a lower 5-year survival rate compared to NHW and H. [Table: see text]

The impact of primary tumor sidedness on survival in early-onset colorectal cancer by stage: A National Veterans Affairs retrospective analysis.

31 Background: The incidence of early-onset colorectal cancer (EOCRC) is rising. Left-sided colorectal cancer (LCC) is associated with better survival and response to therapy compared to right-sided colon cancer (RCC) in the metastatic setting. Current NCCN guidelines recommend the addition of EGFR inhibitors to KRAS/NRAS wild-type metastatic CRC originating from the left-side only. Whether primary tumor sidedness impacts survival in loco-regional disease and in EOCRC is of clinical interest. Methods: Data from the National VA Cancer Cube Registry was studied. 65,940 cases of CRC were diagnosed between 2001 and 2015. EOCRC (2,096 cases) was defined as CRC diagnosis at age &lt;50 years. ICD codes C18 to C20 were used to delineate patients with RCC vs. LCC. RCC was defined as cancer from the cecum to the hepatic flexure (C18.0-C18.3), LCC from the splenic flexure to the rectum (C18.5-18.CRC; C19 &amp; C20). Transverse cancer (C18.4), overlapping and unidentified sites (C18.8; C18.9) were excluded. Results: EOCRC is more likely to originate from the left-side (66.65% LCC in EOCRC vs. 58.77% in the whole CRC dataset). Overall, LCC has better 5-year OS than RCC in Stage I, III and better 1-year OS in stage IV (Table). Stage II RCC has better 5-year OS than LCC (RC 53.39% vs LC 49.28%). In EOCRC, there is no statistically significant difference between LCC and RCC in Stages I-III. Stage IV EOCRC patients with LCC and RCC have a 1-year OS of 73.23% and 59.84%, respectively. Conclusions: EOCRC is more likely than CRC to originate from the left side. In EORCRC patients, LCC is associated with better OS than RCC only in patients with metastatic disease. In the overall population, LCC is associated with better OS in all states except Stage II. The better prognosis of Stage II RCC might be due to the reported high incidence of MSI-high tumors in this subpopulation. [Table: see text]

Contributions of Adenocarcinoma and Carcinoid Tumors to Early-Onset Colorectal Cancer Incidence Rates in the United States.

Early-onset colorectal cancer (EOCRC) incidence rates (IRs) are rising, according to previous cancer registry analyses. However, analysis of histologic subtypes, including adenocarcinoma (the focus of CRC screening and diagnostic testing) and carcinoid tumors (which are classified as "colorectal cancer" in SEER [Surveillance, Epidemiology, and End Results] databases but have a distinct pathogenesis and are managed differently from adenocarcinoma), has not been reported. To assess EOCRC IRs and changes in IRs over time, stratified by histology. Retrospective analysis. Yearly IRs according to SEER 18 data from 2000 to 2016 on age-specific colon-only, rectal-only, and combined-site CRC cases, stratified by histology ("overall" CRC [all histologic subtypes], adenocarcinoma, and carcinoid tumors) and age. 119 624 patients with CRC. IRs per 100 000 population, changes in 3-year average annual IRs (pooled IRs from 2000 to 2002 vs. those from 2014 to 2016), and annual percentage change (APC) in persons aged 20 to 29, 30 to 39, 40 to 49, and 50 to 54 years. The steepest changes in adenocarcinoma 3-year average annual IRs were for rectal-only cases in persons aged 20 to 29 years (+39% [0.33 to 0.46 per 100 000]; P < 0.050) and 30 to 39 years (+39% [1.92 to 2.66 per 100 000]; P < 0.050) and colon-only cases in those aged 30 to 39 years (+20% [3.30 to 3.97 per 100 000]; P < 0.050). Corresponding APCs were 1.6% (P < 0.050), 2.2% (P < 0.050), and 1.2% (P < 0.050), respectively. In persons aged 40 to 49 years, 3-year average annual IRs increased in both colon-only (+13% [12.21 to 13.85 per 100 000]; P < 0.050) and rectal-only (+16% [7.50 to 8.72 per 100 000]; P < 0.050) subsites. Carcinoid tumors were common, representing approximately 4% to 20% of all colorectal and 8% to 34% of all rectal cancer cases, depending on age group and calendar year. Colon-only carcinoid tumors were rare. Colorectal carcinoid tumor IRs increased more steeply than adenocarcinoma in all age groups, thus affecting the contribution of carcinoid tumors to overall cancer cases over time. These changes were driven by rectal subsites and were most pronounced in persons aged 50 to 54 years, in whom rectal carcinoid tumors increased by 159% (2.36 to 6.10 per 100 000) between 2000 to 2002 and 2014 to 2016, compared with 10% for adenocarcinoma (18.07 to 19.84 per 100 000), ultimately accounting for 22.6% of all rectal cancer cases. Population-based data. These findings underscore the importance of assessing histologic CRC subtypes independently. Doing so may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of outcomes from efforts to reduce adenocarcinoma risk, and can guide future research. None.

Abstract PO-223: Racial disparities in early- and late-onset colorectal cancer incidence, 2001- 2016

Abstract Background. Colorectal cancer (CRC) incidence rates have increased in younger individuals worldwide. A recent US study reported increases among both non- Hispanic whites (NHW) and non-Hispanic blacks (NHB), but did not consider other racial/ethnic groups. Thus, we examined the most recent CRC rates for the US by age, race/ethnicity, and anatomic location. Methods. Age-standardized incidence rates (ASR, per 100,000) of CRC were calculated for 2001-2002 through 2015-2016 using the US Cancer Statistics Database, which includes data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results Program. US Cancer Statistics covers the entire US population. Results were cross- classified by age (20-49 [early-onset] and 50-74 years [late-onset]), race/ethnicity (NHW, NHB, Hispanic, American Indian/Alaskan Native [AIAN], Asian/Pacific Islander [API]), and location (proximal, distal, rectal). To examine the change in ASR over time, annual percent change (APC) was calculated using joinpoint regression models. Results. Historically, NHB have had the highest rates of early-onset CRC. However, in 2015-2016, early-onset CRC rates were highest in AIAN (ASR=14.72), followed by NHB (ASR=13.20) and NHW (ASR=12.31). The rate of early-onset proximal colon cancer was highest in NHB (ASR=4.83), which was 62% higher than the rate in NHW (ASR=2.98). Early-onset distal colon and rectal cancer rates were highest in AIAN (ASR=3.98 and 6.43, respectively). Between 2001-2002 and 2015-2016, early-onset CRC rates significantly increased among NHWs (APC=1.62%) and AIAN (APC=3.33%). Racial disparities in incidence of early-onset CRC have decreased between NHB and NHW, due to increasing rates in NHW. Among NHW, early-onset CRC has significantly increased for all CRC locations, with the largest increase for rectal cancer (APC=2.22%). Early-onset rates of rectal cancer also significantly increased for AIAN (APC=4.38%) and Hispanics (APC=0.76%), while rates of proximal colon cancer significantly increased for AIAN (APC=2.21%). Rates of late-onset CRC have significantly decreased in all racial/ethnic groups. However, compared to NHW (ASR=82.48), late-onset CRC rates remain 32% higher in NHB (ASR=108.91) and 18% higher in AIAN (ASR=97.06). Conclusion. Early-onset CRC rates have been increasing, while late-onset CRC rates have decreased. The racial disparity between NHB and NHW in incidence of early-onset CRC has decreased, but this is due to increases in NHW—not decreases in NHB. NHB and AIAN have the highest rates of both early-and late-onset CRC. To counter these trends, research should focus on identifying predictors of early-onset CRC to determine who should be screened prior to age 50 and identify underlying causes of early-onset CRC. Further, ongoing prevention efforts must ensure access to screening colonoscopies for AIAN and NHB. Citation Format: Jessica L. Petrick, Lauren E. Barber, Shaneda Warren Andersen, Andrea A. Florio, Julie R. Palmer, Lynn Rosenberg. Racial disparities in early- and late-onset colorectal cancer incidence, 2001- 2016 [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-223.

Rising incidence of early-onset colorectal cancer - a call to action.

The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity. Early-onset CRCs have differential clinical, pathological and molecular features compared with later-onset CRCs. Certain existing resources can be utilized to elucidate the aetiology of early-onset CRC and inform the development of effective prevention, early detection and therapeutic strategies; however, additional life-course cohort studies spanning childhood and young adulthood, integrated with prospective biospecimen collections, omics biomarker analyses and a molecular pathological epidemiology approach, are needed to better understand and manage this disease entity. In this Perspective, we summarize our current understanding of early-onset CRC and discuss how we should strategize future research to improve its prevention and clinical management.

Rural-urban and racial/ethnic trends and disparities in early-onset and average-onset colorectal cancer.

Incidence rates (IRs) of early-onset colorectal cancer (EOCRC) are increasing, whereas average-onset colorectal cancer (AOCRC) rates are decreasing. However, rural-urban and racial/ethnic differences in trends by age have not been explored. The objective of this study was to examine joint rural-urban and racial/ethnic trends and disparities in EOCRC and AOCRC IRs. Surveillance, Epidemiology, and End Results data on the incidence of EOCRC (age, 20-49 years) and AOCRC (age, ≥50 years) were analyzed. Annual percent changes (APCs) in trends between 2000 and 2016 were calculated jointly by rurality and race/ethnicity. IRs and rate ratios were calculated for 2012-2016 by rurality, race/ethnicity, sex, and subsite. EOCRC IRs increased 35% from 10.44 to 14.09 per 100,000 in rural populations (APC, 2.09; P < .05) and nearly 20% from 9.37 to 11.20 per 100,000 in urban populations (APC, 1.26; P < .05). AOCRC rates decreased among both rural and urban populations, but the magnitude of improvement was greater in urban populations. EOCRC increased among non-Hispanic White (NHW) populations, although rural non-Hispanic Black (NHB) trends were stable. Between 2012 and 2016, EOCRC IRs were higher among all rural populations in comparison with urban populations, including NHW, NHB, and American Indian/Alaska Native populations. By sex, rural NHB women had the highest EOCRC IRs across subgroup comparisons, and this was driven primarily by colon cancer IRs 62% higher than those of their urban peers. EOCRC IRs increased in rural and urban populations, but the increase was greater in rural populations. NHB and American Indian/Alaska Native populations had particularly notable rural-urban disparities. Future research should examine the etiology of these trends.

Genomic and molecular alterations associated with early-onset and adolescent and young adult colorectal cancer

While the incidence of colorectal cancer (CRC) in the US has declined at a pace of 3% annually between 2003 and 2012, there has been an increase in the incidence of early-onset colorectal cancer (EOCRC). The reasons for this increase are unclear. Diet, the environment, the microbiome and alcohol consumption have all been proposed as contributing factors. There is the possibility that EOCRC has a unique biology. Overlapping with the EOCRC age range is CRC in adolescent and young adults (AYA) that share many molecular characteristics with EOCRC. The purpose of this review is to cover current progress in our understanding of the biology of CRC in the context of adolescent and young adult CRC and EOCRC and discuss future directions.

S0320 Rate and Burden of Advanced Colorectal Neoplasia in Adults Approaching the Screening Age: An Opportunity to Reduce the Incidence of Early-Onset Colorectal Cancer

S0320 Rate and Burden of Advanced Colorectal Neoplasia in Adults Approaching the Screening Age: An Opportunity to Reduce the Incidence of Early-Onset Colorectal Cancer

Social Determinants Associated with the Rising Incidence of Early-Onset Colorectal Cancer in the U.S.: A PRISMA Systematic Review

Abstract Objectives To examine the behavioral, socioeconomic, clinical and systemic characteristics of colorectal cancer (CRC) in young adults (19–49 years of age) in the United States (U.S). Methods A systematic literature review was performed using PRISMA methodology. Eleven electronic databases were searched for the extant literature. Study eligibility criteria included colorectal cancer patients in the United States aged 19–49 years. Articles published in peer-reviewed journals in English between January 2009-April 2019 were included. Results Diet, smoking, low physical activity, and gut microbiome changes were identified as modifiable risk factors associated with early-onset colorectal cancer (EOCRC). Racial disparities existed where African American and Hispanic populations had a higher incidence of EOCRC compared to non-Hispanic Whites. Results suggested that delays in EOCRC diagnosis were caused by delays between symptom presentation and appropriate screening. Limitations included use of non-longitudinal cross-sectional analysis, which cannot explain etiologic causes. Conclusions Public health efforts are needed for better adherence to a healthy dietary pattern and increasing physical activity, to bring awareness to young adults and clinicians alike to know the symptoms of EOCRC, and for young people to get screened early in an ethnically-inclusive manner to reduce disparities. Findings suggest more prospective, longitudinal studies need to be conducted and analyzed to study the etiologic factors of EOCRC. Funding Sources The authors have no funding sources to report.

Metabolic syndrome, metabolic comorbid conditions, and risk of early-onset colorectal cancer.

1571 Background: The etiology and contributors to the rising incidence of early-onset colorectal cancer (CRC diagnosed under age 50), driven largely by distal and rectal cancer, remain largely unknown. Metabolic syndrome is associated with higher risk of CRC diagnosed at older ages; however, its association with early-onset CRC remains unclear. Methods: We conducted a nested case-control study among participants aged 18-50 years with ≥2 years of enrollment and prescription drug coverage in the IBM MarketScan Commercial Databases (2006-2015). Incident CRC cases were identified using ICD-9-CM diagnosis codes. Controls without any cancer were identified using frequency matching on age, sex, geographical region, and duration of insurance enrollment. Metabolic syndrome was defined using either ICD-9-CM diagnosis codes or the presence of at least 3 of the following: obesity, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes. In addition to ICD-9-CM codes, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes were also defined based on regular use of medications. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 4,673 early-onset CRC and 40,832 controls were included. Metabolic syndrome was associated with increased risk of early-onset CRC (OR: 1.33, 95% CI 1.16-1.52), after adjusting for a range of potential confounders. The number of metabolic comorbid conditions was positively associated with risk of early-onset CRC in a dose-response fashion. Compared to individuals without any conditions, individuals with 1, 2, ≥3 metabolic conditions had a 13% (OR: 1.13, CI 1.04-1.22), 18% (OR: 1.18, CI 1.07-1.31), and 40% (OR: 1.40, CI 1.22-1.61) higher risk of early-onset CRC (Ptrend&lt;0.001), respectively. These associations were driven by proximal (OR for ≥2 vs 0 metabolic comorbid conditions: 1.40, CI 1.15-1.69) and distal colon cancer, OR ≥2 vs 0: 1.25, CI 1.03-1.53), but not rectal cancer (OR≥2 vs 0: 1.07, CI 0.92-1.24). Conclusions: Metabolic syndrome and metabolic comorbid conditions were associated with increased risk of early-onset CRC, largely driven by proximal and distal colon cancer. Metabolic dysregulations may contribute to the rising incidence of early-onset CRC.

Clinicopathological and molecular biological characteristics of early-onset stage II/III colorectal adenocarcinoma: An analysis of 25 studies with 47,184 patients (pts) in the adjuvant colon cancer end points (ACCENT) database.

4099 Background: Colorectal cancer (CRC) incidence and mortality has decreased since the 1970s but the incidence is increasing in young adults (age 20-49). The incidence of early onset CRC (eoCRC) will keep increasing significantly based on the trends of the SEER CRC registry data. There is limited data suggesting eoCRC may have different behaviors compared to traditional CRC (tCRC, age ≥ 50). Methods: Individual pt data of 47184 stage II/III CRC pts from 25 randomized studies in the ACCENT database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and treatment-related data were summarized by age group. Overall survival (OS), disease-free survival (DFS), recurrence-free rate (RFR), and survival after recurrence (SAR) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for stage, performance status (PS), BMI and grade. Results: Using 5% difference between age groups as clinically meaningful cutoff, eoCRC had similar gender, race, ethnicity, PS, risk group, disease sidedness and T stage as tCRC. eoCRC were less likely overweight (30 vs 36%) and more pts had ≥ 12 lymph nodes resected (63 vs 51%). eoCRC had more frequent dMMR status (18 vs 12%), less BRAF mutations (5 vs 13%), and more dMMR/BRAF wild type (WT) status (17 vs 7%). Overall, eoCRC had better OS, DFS, and SAR, with the most significant differences between the &lt; 30 and &gt; = 70 age groups. Similar results were observed within pMMR pts. eoCRC experienced less hematological side effects, diarrhea, and stomatitis, but had more nausea and/or vomiting. Conclusions: eoCRC have unique characteristics; although statistically significant, the clinical differences in outcomes between eoCRC and tCRC are potentially due to the difference seen in extremely young and old pts. eoCRC have a different adverse events panel compared to tCRC. [Table: see text]