Increasing Incidence of Colorectal Cancer in Younger Adults: A Population-Based Time-Trend Analysis Using the Global Burden of Diseases Database, 1990-2019

Introduction: Colorectal cancer (CRC) accounts for approximately a tenth of all cancer cases and death in the United States (US). Previous data showed that CRC incidence rates have been increasing. However, there are limited data about recent US age and gender-specific CRC incidence trends. The aim of this study was to conduct a time-trend analysis of age and gender-specific CRC incidence rates in the US using the Global Burden Diseases (GBD) 2019 database. Methods: Data was obtained from the GBD 2019 database, an international database that covers ∼100% of CRC diagnosed cases in the US. CRC incidence rates, age-adjusted to the standard US population, were calculated using SEER*Stat software (v.8.4.0.1, National Cancer Institute [NCI]) and were stratified by sex, as reported in the database. Time-trends were estimated as annual percentage change (APC) and average APC (AAPC) using Joinpoint Regression Software (v.4.9.0.1, NCI) utilizing Monte Carlo permutation analysis to generate the simplest trend. Pairwise comparison was conducted between gender-specific trends using the tests of parallelism and coincidence. Age-specific trends were also assessed in two age sub-groups: younger adults aged 15-49 years and older adults aged 50-74 years. A 2-sided P-value cut-off of 0.05 was utilized for statistical significance. Results: 5.53 million patients were diagnosed with CRC in the US between 1990-2019. Overall, CRC incidence rates have been significantly increasing in younger adults (11.1 per 100,000 persons) and decreasing in older adults (136.8 per 100,000 persons) (AAPC= 1.2 vs -0.6; AAPC difference=1.8, P< 0.001). Age-specific trends were neither identical (P< 0.001) nor parallel (P< 0.001), suggesting that CRC incidence rates are different and increasing at a greater rate in younger adults compared to older adults. However, for both men and women (49.4 and 35.2 per 100,000 persons), incidence rates have been decreasing over the past three decades at the same rate (AAPC= -0.5 vs -0.5; AAPC difference= 0, P= 0.1) (Figure 1, Table 1). Conclusion: Our nationwide study shows that CRC incidence trends have increased in younger adults and decreased in older adults over the past three decades. Future studies are needed to evaluate the characteristics of tumors and risk factors associated with the greater increase in CRC in younger adults and the potential impact of screening for colorectal cancer at an earlier age in younger patient populations.Figure 1.: Trend analysis of Colorectal cancer age-standardized incidence rate with age (A) and gender (B) variations from 1990 to 2019. Table 1. - Age and Gender-Specific Trends for Colon and Rectal Cancer (CRC) Incidence: Among Different Age and Gender Groups Incidence Trendsa Age/Gender-specific AAPC difference (95% CI)b Pairwise comparison P-values Time period APC (95% CI) AAPC (95% CI) Age/Gender-specific AAPC difference Coincidencec Parallelismd Gender Male 1990-1994 1.1 (0.2 to 2.0) -0.5 (-0.8 to -0.2) 0 0.126 < 0.0001 < 0.0001 1994-2002 -0.7 (-1.1 to -0.4) 2002-2006 -2.9 (-4.2 to -1.5) 2006-2015 -0.4 (-0.7 to -0.1) 2015-2019 0.7 (-0.3 to 1.6) Female 1990-1994 0.9 (0.1 to 1.8) -0.5 (-0.7 to -0.3) 1994-2002 -0.1 (-0.5 to 0.2) 2002-2006 -2.8 (-4.0 to -1.5) 2006-2019 -0.4 (-0.6 to -0.3) Age 50-74 years 1990-1994 0.8 (0.1 to 1.6) -0.6 (-0.9 to -0.4) -1.8 (-2.4 - -1.2) < 0.001 < 0.0001 < 0.0001 1994-2002 -1.8 (-2.1 to -1.5) 2002-2006 -3.5 (-4.6 to -2.4) 2006-2014 -0.0 (-0.3 to 0.3) 2014-2019 1.5 (0.9 to 2.0) 15-49 years 1990-1994 4.1 (2.8 to 5.6) 1.2 (0.9 to 1.6) 1994-2002 2.4 (1.8 to 3.0) 2002-2017 0.5 (0.3 to 0.7) 2017-2019 -3.2 (-7.3 to -1.0) (a)Time-trends were computed using Joinpoint Regression Program (v4.9.0.1, NCI) with 5 maximum joinpoints allowed (6-line segments). (b) A negative value indicates a greater AAPC in younger compared to older age group. (c) Tests whether age/gender-specific trends were identical. A significant P-value indicates that the trends were not identical (i.e., they had different incidence rates, and the coincidence was rejected). (d) Tests whether age/gender-specific trends were parallel. A significant P-value indicates that the trends were not parallel (i.e., parallelism was rejected).