Introduction

Colorectal cancer (CRC), the third most diagnosed cancer and the second leading cause of cancer-related deaths globally, poses a significant health concern [1]. Recent data from colorectal cancer statistics estimated that in 2023, there would be 153,020 new CRC cases and approximately 52,550 related deaths [2]. Over the past few decades, CRC incidence and mortality rates have witnessed a significant decline due to enhanced screening measures and treatment modalities [3]. However, a concerning shift has emerged, with a growing number of CRC diagnoses occurring in individuals under 50 years of age, known as early-onset CRC (EOCRC) [4, 5]. Currently, this younger demographic accounts for about 10% of all new CRC cases in the USA [6]. A comprehensive systemic review of 40 studies from 12 nations spanning five continents revealed an approximately 30% surge in EOCRC incidence over the past two decades [7]. This trend is significantly influenced by rising incidences in countries such as the USA, Australia, and Canada. Consequently, in 2018, the American Cancer Society (ACS) recommended that CRC screening for average-risk adults start at age 45 [8,9,10].

EOCRC is characterized by primarily left-sided and rectal involvement, increased mucinous and signet ring subtypes, poorer cell differentiation, a higher pathological grade, and a more advanced stage at diagnosis [11, 12]. While genetic syndromes and familial history account for about 30% of EOCRC cases, the majority seem to occur sporadically, and the underlying causes of this increase remain undetermined. Numerous risk factors have been proposed as potential contributors to EOCRC development [13, 14], including socioeconomic status, lifestyle, diet, antibiotic exposure, and intrinsic elements such as genetics, gut microbiota, and oxidative stress from early life [15]. However, the rising incidence of EOCRC cannot be entirely explained by existing CRC risk factors, suggesting that additional EOCRC risk factors may exist that have not yet been identified [15].

Several studies have highlighted significant disparities in EOCRC incidence regarding age, gender, and race. Petrick et al. found that EOCRC rates in the USA are notably higher in American Indians/Alaskan Natives and Blacks compared to Whites, with Blacks experiencing double the rates of EOCRC neuroendocrine tumors compared to Whites [16]. While overall EOCRC incidence is more prevalent in men, women have a higher incidence of distal EOCRC [16]. Additionally, racial disparities negatively impact EOCRC outcomes regardless of socioeconomic status, as demonstrated by Kamath et al. In all socioeconomic subgroups, Black patients with EOCRC had lower overall survival (OS) compared to White patients [17]. Despite these findings, available data on disparities in mortality rates among EOCRC patients is limited. Therefore, this study aimed to identify disparities potentially influencing EOCRC mortality rates, enhance risk assessment tools, and highlight areas necessitating further research. This understanding is crucial for developing targeted interventions and tailored health strategies to address the unique challenges posed by EOCRC and ultimately improve outcomes for this increasingly affected population.

Methods

Data Source

This study utilized the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, a comprehensive online resource designed for epidemiological research [18]. Developed by the CDC, this tool provides broad access to a vast array of public health data for both professionals and the public [19]. Mortality data for the study, specifically “Underlying Cause of Death by Bridged-Race Categories” for the years 2012–2020, were retrieved and downloaded from CDC WONDER. The data included the age-adjusted mortality rate (AAMR) across different gender and racial groups in the USA through 2020. This database, compiled from death certificates from all 50 states and the District of Columbia, contains information on the primary cause of death and demographic data [19]. The aggregated statistics offered by the database include the total number of deaths and crude death rates, stratified by demographic characteristics such as age group, race, gender, race, and more.

Study Population

This research investigated the mortality trend in EOCRC using data from 2012 to 2020. Individuals who died from EOCRC under the age of 50 were identified using the International Classification of Diseases, Tenth Edition (ICD-10) codes [refer to Supplementary material 1: Code table].

Data Collection and Synthesis

Mortality figures and crude rates (the number of deaths per 100,000 individuals) were sourced from the CDC WONDER dataset. The data were organized for analysis using the “Group by” function available on the online interface. Data interpretation and graphical representation were conducted using R 4.2.2 software, with all illustrations generated using the ggplot2 package. This approach allowed for a detailed examination of mortality trends and disparities across different demographic groups, providing a comprehensive overview of EOCRC mortality in the USA during the study period.

Data Privacy and Confidentiality

The study utilized publicly available data from the CDC WONDER database, which is de-identified and aggregated to protect individual privacy. No personal identifying information was accessed or used in this research, ensuring compliance with confidentiality standards and regulations.

Since the data used in this study is publicly available and de-identified, informed consent from individuals was not required. The CDC WONDER database adheres to strict data protection protocols to ensure that personal information is not disclosed.

Results

Crude Mortality Rates

The crude mortality rates for EOCRC from 2012 to 2020 are detailed in Table 1, revealing significant trends and disparities across various demographic groups. The overall crude mortality rate for EOCRC remained relatively stable over the study period, fluctuating marginally between 1.7 and 1.8 per 100,000 individuals. This stability suggests a consistent overall burden of EOCRC mortality within the U.S. population during this timeframe (Fig. 1 and Table 1).

Table 1 Crude mortality rate per 100,000 for the EOCRC
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Fig. 1
figure 1

This chart illustrates the trends in the crude mortality rate of EOCRC in the USA from 2012 to 2020

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Mortality Rates by Sex

The mortality rate for females remained relatively constant, varying between 1.5 and 1.6 per 100,000. There was no significant change observed over the study period. The mortality rate for males was consistently higher than for females, ranging from 1.9 to 2.0 per 100,000. A slight increase was noted, from 1.9 in 2012 to 2.0 in 2018, and this rate remained steady through 2020 (Fig. 2).

Fig. 2
figure 2

Crude mortality rate of EOCRC in the USA from 2012 to 2020, sub-grouped by gender

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Mortality Rates by Age Group

The mortality rate for individuals aged 20–29 years demonstrated minor fluctuations, ranging from 0.28 to 0.34 per 100,000. The rate was highest in 2012 and 2020 at 0.34, with a slight decrease observed in the intervening years, reaching its lowest point in 2018 at 0.28. For those aged 30–39 years, the mortality rate exhibited slight variability, ranging from 1.67 to 1.86 per 100,000. The highest rate occurred in 2018 at 1.86, showing a general upward trend from 2014 onwards, with a minor dip in 2019. The 40–49 age group experienced the highest mortality rates, ranging from 6.34 to 6.99 per 100,000. There was a gradual increase over the years, peaking in 2018 at 6.99, with a slight decrease to 6.94 by 2020 (Fig. 3).

Fig. 3
figure 3

Crude mortality rate of EOCRC in the USA from 2012 to 2020, sub-grouped by age group

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Mortality Rates by Racial Category

The mortality rate for White individuals was stable, remaining around 1.7 to 1.8 per 100,000 throughout the study period. This group exhibited higher mortality rates compared to Whites, with rates fluctuating between 2.0 and 2.2 per 100,000. The highest rate was observed in 2014 at 2.2, with a slight decline in 2019 (1.9) before increasing again in 2020 (2.1).

The mortality rate for Asian or Pacific Islander individuals was lower, ranging from 1.1 to 1.4 per 100,000. There was a gradual increase from 1.1 in 2014 to 1.4 in 2020. This group showed considerable variability in mortality rates, ranging from 0.6 to 1.4 per 100,000. The highest rate was in 2016 (1.4), with a notable dip in 2017 (0.6) and a gradual increase thereafter (Fig. 4).

Fig. 4
figure 4

This figure illustrates the trend in the crude mortality rate of EOCRC in the USA from 2012 to 2020, with data segmented according to different racial groups

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Mortality Rates by Geography

Mortality rates were not available for some of the states in the USA. Higher mortality rates were observed in Mississippi and Alabama, while the lowest mortality rate was observed among the Midwest regions (Fig. 5).

Fig. 5
figure 5

This illustrates the trend in the crude mortality rate of EOCRC in the USA from 2012 to 2020, sub-grouped by states

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AAMR by Racial Groups

Table 2 presents the AAMR for different racial groups in the USA from 2012 to 2020. Throughout the study period, Black or African American individuals consistently exhibited the highest AAMR, ranging from 18.5 to 22.3 per 100,000 population, followed by White individuals with rates ranging from 14.6 to 16.6 per 100,000. American Indian or Alaska Native and Asian or Pacific Islander groups generally showed lower AAMRs compared to Black or African American and White populations.

Table 2 The AAMR across different racial groups in the USA through 2020
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AAMR by Gender Groups

As illustrated in Table 3, there has been a notable decrease in the AAMR for both men and women over the analyzed period. In 2012, the AAMR for men stood at 20.6 (20.3–20.8), declining to 18.1 (17.9–18.3) by 2020. Likewise, for women, the AAMR decreased from 14.1 (14.0–14.3) in 2012 to 12.2 (12.1–12.4) in 2020. This longitudinal examination highlights an overall enhancement in health outcomes for both genders over time. However, despite this positive trend, the data consistently reveal higher mortality rates for men compared to women throughout the evaluated period, underscoring the necessity for further investigation into the underlying factors contributing to this disparity.

Table 3 The AAMR across different gender groups in the USA through 2020
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Discussion

This study investigated racial, gender and geographical disparities in EOCRC in the US, using data from the CDC WONDER database. This comprehensive resource provided extensive information on EOCRC mortality rates from 2012 to 2020, allowing for a robust analysis of trends and disparities across demographic groups. Our findings indicated that the overall mortality rate for EOCRC has remained relatively stable over the past decade, with a minor increase from 1.7 per 100,000 individuals in 2012 to 1.8 per 100,000 individuals in 2020. This stability is consistent with existing literature that suggests an escalating incidence of EOCRC, especially in high-income countries [20, 21]. The constancy in mortality rates aligns with studies suggesting that advancements in screening, diagnosis, and management of EOCRC might be contributing factors [22,23,24].

Significant disparities were evident when data were examined according to gender, age, and racial category. Men with EOCRC consistently exhibited higher mortality rates than women. This observation is consistent with prior studies, such as Rawla et al., which documented elevated colorectal cancer incidence and mortality rates in males [3]. Such findings suggest that men may inherently face higher CRC susceptibility and a less favorable prognosis, potentially stemming from an interplay of biological, environmental, and lifestyle determinants [3, 25]. The underlying reasons behind this persistent gender disparity in EOCRC mortality remain unclear, highlighting the need for deeper exploration.

A dramatic rise in the mortality rate was observed among the age group of 20 to 50 years, particularly in the 40–49 years category. This supports the current recommendation by the American Cancer Society (ACS) to lower the starting age for average-risk adults to 45 years for CRC screening [9, 26]. Timely screening has been proven to be an effective strategy in reducing mortality associated with CRC [27, 28]. Therefore, increasing awareness and advocating for early and regular screening could help curb the rising mortality in this age group [29].

Racial disparities were also prominent in our study. African Americans were found to have the highest EOCRC mortality rate compared to other ethnic groups. This is consistent with previous research that has highlighted racial disparities in CRC incidence and outcomes [30]. This racial disparity could be attributed to a multitude of factors, including socio-economic status, access to healthcare, health behavior, and potential genetic predispositions [17]. Efforts should be directed to reduce this racial disparity through the implementation of targeted public health initiatives and policies that promote equal access to screening and healthcare services.

Our study also found geographical disparities in EOCRC mortality across different states. Higher mortality rates were observed in Mississippi and Alabama, while the Midwest regions recorded lower mortality rates. Previous studies have reported similar geographic disparities, which might be influenced by regional differences in healthcare access, environmental factors, socio-economic status, and lifestyle habits [31].

Strengths and Limitations

One of the key strengths of this study is the utilization of the CDC WONDER database, which is a reliable and comprehensive source of mortality data. The long study period (2012–2020) allows for a thorough examination of trends over time. Additionally, the study’s stratification of data by age, sex, and race provides a detailed understanding of the disparities in EOCRC mortality, highlighting areas in need of targeted interventions. Despite its strengths, the study has several limitations. The descriptive nature of the analysis and potential underestimation of mortality rates in the CDC WONDER database, which relies on the accurate reporting and coding of death certificates, are notable constraints. Additionally, our study focused solely on mortality rates and did not consider the incidence or survival rates of EOCRC. Due to the suppression criteria of the CDC WONDER, death counts under 10 were not accessible from the dataset, potentially influencing our results.

Future Directions

The findings of this EOCRC study sound a critical alarm, highlighting the urgent need for action on several aspects. With men consistently facing higher mortality rates, it is important to target research efforts toward gender-specific determinants of the disease and tailor interventions accordingly. Racial disparities necessitate immediate actions and modifications in healthcare policies to ensure equitable healthcare access across all racial and ethnic groups. The surge in mortality rates among those aged 40–49 also demands a prompt reassessment of CRC screening guidelines. Moreover, geographical disparities highlight the pressing need for region-specific healthcare strategies, taking into account unique local factors affecting health outcomes. Finally, the healthcare community, policymakers, and stakeholders must collaborate together, translating these findings into concrete, targeted actions that tackle EOCRC disparities head-on.

Conclusion

In conclusion, our study highlights disparities in EOCRC mortality trends in the USA. While overall mortality rates remained stable, significant disparities by gender, age, race, and geography were evident. These findings highlight the urgent need for targeted interventions to address these disparities. Addressing these disparities through targeted public health strategies, policy changes, and increased awareness can lead to better outcomes and reduce the burden of EOCRC in the USA. Future research should focus on the factors driving these disparities, with an emphasis on the roles of genetics, lifestyle, and environmental factors.