Keywords
America - mortality - colorectal cancer - sex
Introduction
Colorectal cancer (CRC) is a malignant neoplasm arising from the epithelial cells
of the colon or rectum, representing one of the most prevalent and lethal forms of
cancer worldwide.[1] Histologically, many CRC cases are adenocarcinomas, originating from glandular epithelial
cells. Less common subtypes include mucinous adenocarcinomas, characterized by abundant
extracellular mucin production, and signet-ring cell carcinomas, an aggressive variant
with poor prognosis.[1] Other rare histological subtypes, such as neuroendocrine tumors and squamous cell
carcinomas, account for a small proportion of cases but often exhibit distinct biological
behaviors and clinical outcomes.[1]
The development of CRC is influenced by a multifactorial interplay of genetic and
environmental risk factors.[2] Familial syndromes, such as Lynch syndrome and familial adenomatous polyposis, significantly
increase the lifetime risk of CRC due to inherited genetic mutations.[2] Lifestyle-related factors, including a diet high in red and processed meats, low
fiber intake, obesity, physical inactivity, and excessive alcohol consumption, contribute
to sporadic CRC cases.[2] Chronic inflammatory conditions, such as inflammatory bowel disease (ulcerative
colitis and Crohn's disease), are also associated with an increased risk, highlighting
the role of persistent inflammation in carcinogenesis.[2]
Clinically, CRC presents with a broad spectrum of symptoms, often depending on tumor
location and disease stage.[3] Early-stage cases may remain asymptomatic or cause nonspecific gastrointestinal
complaints, such as changes in bowel habits, mild abdominal discomfort, or intermittent
rectal bleeding.[3] As the disease progresses, symptoms become more pronounced, including hematochezia
or melena, iron-deficiency anemia, unintentional weight loss, and bowel obstruction
in advanced cases.[3] The insidious nature of CRC underscores the critical importance of early detection
through screening programs, which significantly improve prognosis and survival rates.[3]
The incidence of CRC has been rising globally, with variations across different geographic
regions.[4] While high-income countries have observed a stabilization or decline in mortality
rates due to improved screening and treatment strategies, low- and middle-income regions
continue to experience an increasing burden.[4] This trend has significant social and economic implications, as CRC-related morbidity
and mortality impose substantial healthcare costs and productivity losses.[4] The shifting epidemiology of CRC necessitates comprehensive public health interventions
aimed at prevention, early diagnosis, and equitable access to treatment.[4]
Given the growing impact of CRC on public health, it is crucial to examine temporal
trends in mortality rates to better understand the epidemiological dynamics of the
disease.[1]
[2] Investigating these trends across the Americas allows for the identification of
regional disparities and the effectiveness of preventive and therapeutic strategies.[2]
[3] Such studies provide valuable insights for policymakers and healthcare professionals,
facilitating data-driven decision-making to enhance cancer control measures, optimize
resource allocation, and ultimately reduce CRC-related mortality.[1]
[2]
[3]
[4] So, this study was developed with the aim to evaluate the temporal trends of CRC
mortality rates across the American continent.
Materials and Methods
Study Design
This research was designed as a retrospective, populational with quantitative approach
study.
Data Source
All data used in this study were obtained from the Pan American Health Organization
(PAHO), available at the following link:
https://www.paho.org/en
. In case, PAHO is the oldest international health organization in the world, acting
as a regional agent of the World Health Organization (WHO) in the Americas. It specializes
in health promotion, disease prevention, epidemiological analysis, among other actions
in the location.
Data Collection
Data were collected from the PAHO's archive and published on January 15th, 2025, on
the aforementioned website. The collection was performed manually by the author of
this research by transposing the data into Excel ® spreadsheets. The Data were stratified
by country's origin, reported year, individual's sex, and the reported age-adjusted
mortality rates for 100,000 individuals. The study's time draft was chosen as the
one between 2000 and 2019 since it was the unique time range disponible in the data.
Data Analysis
An annual percentage change (APC) was calculated with the Jointpoint software 5.0
® to evaluate the temporal trends of CRC mortality rates.
The APC is calculated using a regression model where time is treated as an independent
variable, and the natural logarithm of the observed rates is utilized as the dependent
variable. This approach involves fitting the natural logarithm of each observation
to a straight line, with the slope of this line representing the rate of change over
time. The APC quantifies the average percentage change per year within the specified
time frame, providing a standardized measure to evaluate trends.
The 95% confidence interval was calculated for the evaluated APCs. For statistically
significant confidence intervals (p-values < 0.05), a positive APC suggests an increasing
trend, while a negative APC indicates a decreasing trend; in parallel, a non-significant
confidence interval (p-value ≥ 0.05) suggests a stationary trend.
Results
Both Sexes
In South America, between 2000 and 2012, mortality rates increased significantly (APC:
0.62; 95%CI: 0.51 - 1.07; p-value: < 0.01). From 2012 to 2019, the trend was not significant
(APC: 0.17; 95%CI: −0.76 - 0.41; p-value: 0.43). In Central America, between 2000
and 2003, there was a marked increase (APC: 4.26; 95%CI: 3.42 - 5.53; p-value: < 0.01),
followed by a decline from 2003 to 2006 (APC: −1.39; 95%CI: −2.05 - −0.12; p-value:
0.03). From 2006 to 2014, rates increased again (APC: 1.86; 95%CI: 1.60 - 2.35; p-value: < 0.01),
but then decreased between 2014 and 2019 (APC: −0.63; 95%CI: −1.32 - −0.09; p-value:
0.02). In North America, mortality rates decreased significantly from 2000 to 2009
(APC: −1.51; 95%CI: −2.59 - −1.24; p-value: < 0.01). From 2009 to 2019, the decline
was not statistically significant (APC: −1.01; 95%CI: −1.27 - 0.19; p-value: 0.07).
From a whole American perspective, the period 2000–2003 saw an increase (APC: 2.28;
95%CI: 1.69 - 3.33; p-value: < 0.01), followed by a decline from 2003 to 2006 (APC:
−0.83; 95%CI: −1.30 - 0.07; p-value: 0.08). From 2006 to 2014, there was an increase
(APC: 1.13; 95%CI: 0.94 - 1.64; p-value: < 0.01), but rates decreased from 2014 to
2019 (APC: −0.45; 95%CI: −0.98 - −0.06; p-value: 0.02) - [Table 1] and [Fig. 1].
Table 1
Temporal trends in age-adjusted mortality rates by colorectal cancer by 100,000 individuals
from both sexes
|
Cohort
|
Segment
|
Lower Endpoint
|
Upper Endpoint
|
APC
|
Lower CI
|
Upper CI
|
P-Value
|
|
South America
|
1
|
2000
|
2012
|
0.62
|
0.51
|
1.07
|
< 0.01
|
|
South America
|
2
|
2012
|
2019
|
0.17
|
−0.76
|
0.41
|
0.43
|
|
Central America
|
1
|
2000
|
2003
|
4.26
|
3.42
|
5.53
|
< 0.01
|
|
Central America
|
2
|
2003
|
2006
|
−1.39
|
−2.05
|
−0.12
|
0.03
|
|
Central America
|
3
|
2006
|
2014
|
1.86
|
1.60
|
2.35
|
< 0.01
|
|
Central America
|
4
|
2014
|
2019
|
−0.63
|
−1.32
|
−0.09
|
0.02
|
|
North America
|
1
|
2000
|
2009
|
−1.51
|
−2.59
|
−1.24
|
< 0.01
|
|
North America
|
2
|
2009
|
2019
|
−1.01
|
−1.27
|
0.19
|
0.07
|
|
Total
|
1
|
2000
|
2003
|
2.28
|
1.69
|
3.33
|
< 0.01
|
|
Total
|
2
|
2003
|
2006
|
−0.83
|
−1.30
|
0.07
|
0.08
|
|
Total
|
3
|
2006
|
2014
|
1.13
|
0.94
|
1.64
|
< 0.01
|
|
Total
|
4
|
2014
|
2019
|
−0.45
|
−0.98
|
−0.06
|
0.02
|
Fig. 1 Temporal trends in age-adjusted mortality rates by colorectal cancer by 100,000 individuals
from both sexes.
Women
In South America, between 2000 and 2019, mortality rates increased significantly (APC:
0.29; 95%CI: 0.13 - 0.45; p-value: < 0.01). In Central America, a sharp increase occurred
between 2000 and 2003 (APC: 5.44; 95%CI: 3.81 - 7.45; p-value: < 0.01). The trend
between 2003 and 2008 was not significant (APC: −0.52; 95%CI: −2.12 - 0.31; p-value:
0.16). From 2008 to 2014, mortality increased (APC: 2.25; 95%CI: 1.65 - 3.88; p-value: < 0.01),
followed by a decrease from 2014 to 2019 (APC: −1.07; 95%CI: −2.08 - −0.34; p-value: < 0.01).
In North America, there was a significant decrease from 2000 to 2009 (APC: −1.57;
95%CI: −2.67 - −1.28; p-value: < 0.01). The decline from 2009 to 2019 was not statistically
significant (APC: −0.89; 95%CI: −1.16 - 0.29; p-value: 0.08). On the all-American
continent point of view, between 2000 and 2003, mortality rates increased (APC: 3.17;
95%CI: 2.33 - 4.49; p-value: < 0.01), followed by a significant decline from 2003
to 2006 (APC: −1.48; 95%CI: −2.12 - −0.22; p-value: 0.01). The period 2006–2014 saw
an increase (APC: 1.20; 95%CI: 0.95 - 2.06; p-value: < 0.01), but a decline was observed
from 2014 to 2019 (APC: −0.66; 95%CI: −1.47 - −0.13; p-value: 0.01) - [Table 2] and [Fig. 2].
Table 2
Temporal trends in age-adjusted mortality rates by colorectal cancer by 100,000 individuals
from women
|
Cohort
|
Segment
|
Lower Endpoint
|
Upper Endpoint
|
APC
|
Lower CI
|
Upper CI
|
P-Value
|
|
South Americas
|
1
|
2000
|
2019
|
0.29
|
0.13
|
0.45
|
< 0.01
|
|
Central America
|
1
|
2000
|
2003
|
5.44
|
3.81
|
7.45
|
< 0.01
|
|
Central America
|
2
|
2003
|
2008
|
−0.52
|
−2.12
|
0.31
|
0.16
|
|
Central America
|
3
|
2008
|
2014
|
2.25
|
1.65
|
3.88
|
< 0.01
|
|
Central America
|
4
|
2014
|
2019
|
−1.07
|
−2.08
|
−0.34
|
< 0.01
|
|
North America
|
1
|
2000
|
2009
|
−1.57
|
−2.67
|
−1.28
|
< 0.01
|
|
North America
|
2
|
2009
|
2019
|
−0.89
|
−1.16
|
0.29
|
0.08
|
|
Total
|
1
|
2000
|
2003
|
3.17
|
2.33
|
4.49
|
< 0.01
|
|
Total
|
2
|
2003
|
2006
|
−1.48
|
−2.12
|
−0.22
|
0.01
|
|
Total
|
3
|
2006
|
2014
|
1.20
|
0.95
|
2.06
|
< 0.01
|
|
Total
|
4
|
2014
|
2019
|
−0.66
|
−1.47
|
−0.13
|
0.01
|
Fig. 2 Temporal trends in age-adjusted mortality rates by colorectal cancer by 100,000 individuals
from women.
Men
In South America, between 2000 and 2010, there was a significant increase in mortality
rates (APC: 1.12; 95%CI: 0.88 - 1.57; p-value: < 0.01). From 2010 to 2019, the trend
was not significant (APC: 0.21; 95%CI: −0.32 - 0.48; p-value: 0.28). In Central America,
mortality rates increased significantly from 2000 to 2019 (APC: 0.99; 95%CI: 0.71
- 1.28; p-value: < 0.01). In North America, there was a consistent decline from 2000
to 2019 (APC: −1.36; 95%CI: −1.51 - −1.21; p-value: < 0.01). Over the whole continent,
between 2000 and 2003, rates increased (APC: 1.44; 95%CI: 0.48 - 2.83; p-value: < 0.01).
The trend between 2003 and 2006 was not significant (APC: −0.57; 95%CI: −1.19 - 1.50;
p-value: 0.23). From 2006 to 2011, a borderline increase was observed (APC: 1.59;
95%CI: −0.02 - 2.51; p-value: 0.05), followed by a non-significant trend from 2011
to 2019 (APC: 0.07; 95%CI: −0.22 - 0.36; p-value: 0.56) - [Table 3] and [Fig. 3].
Table 3
Temporal trends in age-adjusted mortality rates by colorectal cancer by 100,000 individuals
from men
|
Cohort
|
Segment
|
Lower Endpoint
|
Upper Endpoint
|
APC
|
Lower CI
|
Upper CI
|
P-Value
|
|
South America
|
1
|
2000
|
2010
|
1.12
|
0.88
|
1.57
|
< 0.01
|
|
South America
|
2
|
2010
|
2019
|
0.21
|
−0.32
|
0.48
|
0.28
|
|
Central Americas
|
1
|
2000
|
2019
|
0.99
|
0.71
|
1.28
|
< 0.01
|
|
North Americas
|
1
|
2000
|
2019
|
−1.36
|
−1.51
|
−1.21
|
< 0.01
|
|
Total
|
1
|
2000
|
2003
|
1.44
|
0.48
|
2.83
|
< 0.01
|
|
Total
|
2
|
2003
|
2006
|
−0.57
|
−1.19
|
1.50
|
0.23
|
|
Total
|
3
|
2006
|
2011
|
1.59
|
−0.02
|
2.51
|
0.05
|
|
Total
|
4
|
2011
|
2019
|
0.07
|
−0.22
|
0.36
|
0.56
|
Fig. 3 Temporal trends in age-adjusted mortality rates by colorectal cancer by 100,000 individuals
from men.
Countries
An evaluation of CRC mortality trends by each American country analyzed can be assessed
in the following link:
https://docs.google.com/spreadsheets/d/1oYDkZUDw0P47aLWfnFWm72QIjDfJSr7gZEX6B2ZPuYE/edit?usp=sharing
.
Discussion
For both sexes, colorectal cancer mortality rates have shown increasing trends in
South and Central America, with fluctuations, while North America has experienced
a general decline. Among women, South and Central America showed increasing trends,
but North America exhibited a decreasing pattern. Among men, South and Central America
saw rising mortality rates, whereas North America showed a consistent decline.
The observed trends in colorectal cancer (CRC) mortality across different regions
highlight the complex interplay of social, economic, and healthcare-related factors
in shaping the burden of this disease.[5]
[6] In Latin America and the Caribbean, CRC mortality rates have increased significantly
in several countries, while nations such as Argentina and Uruguay have experienced
declines. These divergent patterns can be attributed to disparities in healthcare
infrastructure, screening programs, and public health policies.[5]
[6] Uruguay, for instance, has implemented robust CRC screening programs, which likely
contributed to the reduction in mortality, particularly among women aged 50 to 74
years.[5] Conversely, in countries where mortality has increased, limited access to early
diagnosis and treatment remains a critical challenge.[7]
Economic development and healthcare accessibility play crucial roles in CRC mortality
trends.[8]
[9] High-income countries have generally experienced stable or declining CRC mortality
rates due to the widespread implementation of early detection strategies, improved
treatments, and increased public awareness.[8] In contrast, middle- and low-income regions continue to face rising CRC mortality
due to limited preventive measures and inadequate healthcare resources.[9] For example, in Mexico, mortality rates increased from 3.9 to 4.8 per 100,000 inhabitants
between 2000 and 2012, with the highest rates observed in Baja California, Baja California
Sur, and Sonora.[8] These trends likely reflect the unequal distribution of medical facilities, delays
in diagnosis, and lifestyle changes associated with urbanization, including increased
consumption of processed foods and decreased physical activity.[8]
[9]
Sex-based differences in CRC mortality patterns suggest that biological and behavioral
factors significantly influence outcomes.[10]
[11] Women have historically exhibited lower CRC incidence and mortality rates compared
with men, potentially due to the protective effects of estrogen, which modulates immune
responses and reduces chronic inflammation.[10] Additionally, differences in dietary habits, smoking prevalence, and occupational
exposures contribute to varying risks between sexes.[10] However, in some regions, female CRC mortality has increased more sharply than in
men, as observed in Brazil, where CRC mortality rose from 5.60 to 7.98 per 100,000
inhabitants between 2005 and 2014, disproportionately affecting women in the South
and Southeast regions.[11] This may reflect shifting dietary patterns, increased obesity rates, and delayed
diagnosis in female patients.[11]
The role of inflammatory pathways, cytokine activity, and genetic predispositions
further explains sex-based disparities in CRC mortality.[12]
[13] Estrogen is known to regulate inflammatory cytokines such as IL-6 and TNF-α, which
are implicated in colorectal carcinogenesis. In postmenopausal women, the decline
in estrogen levels may lead to increased inflammation, contributing to higher CRC
risk.[12] Conversely, men generally exhibit higher systemic inflammation and oxidative stress
levels, factors that exacerbate tumor progression1.[3] The notable decline in CRC mortality in Uruguayan women aged 50–74 years suggests
that gender-targeted screening programs and healthcare interventions may effectively
reduce mortality, underscoring the need for similar strategies in other high-risk
populations.[5]
Another crucial factor influencing CRC mortality trends is population aging.[14] As life expectancy increases, a larger proportion of the population enters age groups
at higher risk for CRC, leading to an overall rise in mortality despite advances in
treatment.[14] In Barranquilla, Colombia, CRC mortality nearly tripled between 1985 and 2020, with
59.6% of recorded deaths occurring in women.[14] This trend reflects not only an aging population but also delayed detection and
suboptimal management of CRC cases in older adults.[14] Additionally, the study highlighting a relative decrease in CRC-related deaths alongside
an increase in non-cancer causes of mortality among CRC patients suggests that cardiovascular
disease and other comorbidities play an increasing role in long-term patient outcomes.[14]
Globally, regional disparities in CRC mortality emphasize the need for targeted public
health initiatives.[15]
[16] In 2012, the highest mortality rates were recorded in Central and Eastern Europe,
while the lowest rates were observed in the Middle Division of Africa.[15] These discrepancies highlight the impact of socioeconomic factors, dietary patterns,
and healthcare access.[15] European countries with high CRC mortality may be experiencing aging populations
and lifestyle-related risk factors, whereas, in Africa, lower CRC mortality might
be due to differences in diet, genetic predisposition, or underreporting due to inadequate
cancer surveillance systems.[16]
Looking forward, the future trajectory of CRC mortality will be shaped by advancements
in early detection, personalized treatment approaches, and population-level preventive
measures.[17] Improved screening technologies, such as liquid biopsy and molecular biomarker-based
tests, hold promise for enhancing early diagnosis and treatment precision.[17] Additionally, expanding access to screening in underserved regions will be essential
for mitigating mortality disparities.[17] Public health campaigns promoting healthier diets, increased physical activity,
and smoking cessation can further reduce CRC incidence and mortality in high-risk
populations.[17]
Finally, ongoing epidemiological surveillance is crucial for understanding the evolving
burden of CRC and informing evidence-based policy decisions.[18] Investigating temporal trends in CRC mortality across the Americas provides valuable
insights into the effectiveness of national cancer control programs and healthcare
investments.[18] By identifying successful strategies in countries with declining mortality and addressing
barriers in regions with rising trends, policymakers can implement targeted interventions
to reduce CRC-related deaths and improve cancer outcomes on a global scale.[18] As the burden of CRC continues to rise in certain regions, a coordinated, multi-sectoral
approach will be necessary to bridge healthcare disparities and enhance survival rates
for all populations.[18]
This study presents several strengths that enhance its reliability and significance.
First, by utilizing mortality data from the Pan American Health Organization (PAHO),
the research ensures a comprehensive and standardized dataset covering multiple countries
across the Americas. The extended study period (2000–2019) allows for an in-depth
evaluation of long-term trends, providing valuable insights into epidemiological shifts
over time. Moreover, the application of the Joinpoint regression model ensures a robust
and statistically rigorous analysis of temporal mortality trends, allowing for the
precise identification of changes in mortality patterns. Finally, stratification by
sex enables a more nuanced understanding of potential disparities, contributing to
the growing body of knowledge on sex-related differences in colorectal cancer epidemiology.
Despite its strengths, this study has some limitations that should be acknowledged.
First, the reliance on secondary data from PAHO means that the accuracy of the findings
is dependent on the completeness and quality of the original data sources, which may
vary between countries. Additionally, potential discrepancies in death certification
practices and cancer registry coverage across different regions may introduce bias
in the reported mortality rates. Another limitation is the inability to assess individual-level
risk factors such as genetic predisposition, lifestyle habits, or access to healthcare,
which could provide deeper insights into the observed trends. Lastly, the study does
not account for potential improvements in diagnostic techniques or treatment strategies
over time, which could influence mortality trends independently of epidemiological
shifts.
Conclusions
This study provides a comprehensive analysis of colorectal cancer mortality trends
in the Americas, highlighting both increasing and decreasing patterns in different
countries. The observed trends are likely influenced by a combination of demographic,
socioeconomic, and healthcare-related factors, emphasizing the importance of continued
investments in screening programs, early detection initiatives, and equitable access
to high-quality treatment. The findings also underscore notable sex-based disparities,
suggesting potential biological and behavioral contributors to colorectal cancer outcomes.
As colorectal cancer remains a significant public health concern, future research
should focus on understanding the interplay between policy measures, healthcare access,
and disease burden to develop more effective prevention and control strategies.
Bibliographical Record
Lucas Casagrande Passoni Lopes. Colorectal Cancer Mortality Across the American Continent:
Temporal Trends. Journal of Coloproctology 2025; 45: s00451809671.
DOI: 10.1055/s-0045-1809671
