Title: Global burden, trends, and risk factors of early-onset and late-onset colorectal cancer from
1990 to 2021, with projections to 2040: A population-based study
Version: 0 Date: 10 Mar 2025
Reviewer's report:
General comments:
This is a very interesting and well-written manuscript containing a lot of important data. The
authors do a very good job summarizing such a large amount of information. Despite the large
number of tables and figures, the manuscript is easy to follow. Specific comments are given
below. One minor general comment is to check for consistent use of abbreviations; for example,
colorectal cancer is sometimes written out and sometimes abbreviated.
Specific comments:
1. Introduction: The text says ‘Currently, most countries have established age 50 as the threshold
for initiating colonoscopy screening2.’ – this is not accurate regarding the age and the modality.
Very few countries use colonoscopy as the main screening tool and I’m not sure that the majority
start at aged 50.
2. Introduction: The text says ‘Additionally, some scholars have suggested that the promotion of
colonoscopy screening in individuals under 50 may lead to an increase in EOCRC incidence due
to earlier detection15’ – which countries are promoting colonoscopy screening in those younger
than 50? This needs to be clearly stated rather than just a reference given.
3. Methods: The text says ‘This study analyzed risk factors with demonstrated causal
relationships with EOCRC, including dietary (low intake of milk, calcium, and fiber, high intake
of red and processed meats), behavioural (alcohol consumption, smoking, and low physical
activity), and metabolic factors (high body mass index and high fasting plasma glucose’ – I don’t
think there is evidence for all of these variables being causally associated with EOCRC?
4. Methods: The text says ‘All methods adhered to relevant guidelines and regulations.’ It is
unclear what the authors are referring to here – should be more specific.
5. Methods: need to be more clear on how the modifiable risk factors were selected.
6. Table S12 – unclear how this table is ordered?
7. Table S12 – unclear what ‘epidemiological changes’ means?
8. Results, Section 3.5: be clear that the statistics in this section refer to 2021 rather than 1990.
9. Results, diet and lifestyle factors: it would help to have a clear explanation of how values for
these variables are determined on a country-wide basis.
10. Discussion: The text says ‘For young individuals, using risk scores to identify high-risk
populations could reduce the burden of colonoscopy,’ – screening does not have to rely on
colonoscopy, the text should reflect this.
11. Discussion: The text says ‘Moreover, the similar risk factors for EOCRC and LOCRC
suggest that unified prevention strategies could be effective’ – I’m not sure this is an evidence-
based statement. There is insufficient data on the aetiology of EOCRC.
12. Discussion: lacks information on why certain countries have the highest or lowest statistic.
Please add some discussion on this.
Title: Global burden, trends, and risk factors of early-onset and late-onset colorectal cancer from
1990 to 2021, with projections to 2040: A population-based study
Version: 0 Date: 10 Mar 2025
Reviewer's report:
General comments:
This is a very interesting and well-written manuscript containing a lot of important data. The
authors do a very good job summarizing such a large amount of information. Despite the large
number of tables and figures, the manuscript is easy to follow. Specific comments are given
below. One minor general comment is to check for consistent use of abbreviations; for example,
colorectal cancer is sometimes written out and sometimes abbreviated.
Specific comments:
1. Introduction: The text says ‘Currently, most countries have established age 50 as the threshold
for initiating colonoscopy screening2.’ – this is not accurate regarding the age and the modality.
Very few countries use colonoscopy as the main screening tool and I’m not sure that the majority
start at aged 50.
2. Introduction: The text says ‘Additionally, some scholars have suggested that the promotion of
colonoscopy screening in individuals under 50 may lead to an increase in EOCRC incidence due
to earlier detection15’ – which countries are promoting colonoscopy screening in those younger
than 50? This needs to be clearly stated rather than just a reference given.
3. Methods: The text says ‘This study analyzed risk factors with demonstrated causal
relationships with EOCRC, including dietary (low intake of milk, calcium, and fiber, high intake
of red and processed meats), behavioural (alcohol consumption, smoking, and low physical
activity), and metabolic factors (high body mass index and high fasting plasma glucose’ – I don’t
think there is evidence for all of these variables being causally associated with EOCRC?
4. Methods: The text says ‘All methods adhered to relevant guidelines and regulations.’ It is
unclear what the authors are referring to here – should be more specific.
5. Methods: need to be more clear on how the modifiable risk factors were selected.
6. Table S12 – unclear how this table is ordered?
7. Table S12 – unclear what ‘epidemiological changes’ means?
8. Results, Section 3.5: be clear that the statistics in this section refer to 2021 rather than 1990.
9. Results, diet and lifestyle factors: it would help to have a clear explanation of how values for
these variables are determined on a country-wide basis.
10. Discussion: The text says ‘For young individuals, using risk scores to identify high-risk
populations could reduce the burden of colonoscopy,’ – screening does not have to rely on
colonoscopy, the text should reflect this.
11. Discussion: The text says ‘Moreover, the similar risk factors for EOCRC and LOCRC
suggest that unified prevention strategies could be effective’ – I’m not sure this is an evidence-
based statement. There is insufficient data on the aetiology of EOCRC.
12. Discussion: lacks information on why certain countries have the highest or lowest statistic.
Please add some discussion on this.
Please review this paper.
user
Title: Global burden, trends, and risk factors of early-onset and late-onset colorectal cancer from
1990 to 2021, with projections to 2040: A population-based study
Version: 0 Date: 10 Mar 2025
Reviewer's report:
General comments:
This is a very interesting and well-written manuscript containing a lot of important data. The
authors do a very good job summarizing such a large amount of information. Despite the large
number of tables and figures, the manuscript is easy to follow. Specific comments are given
below. One minor general comment is to check for consistent use of abbreviations; for example,
colorectal cancer is sometimes written out and sometimes abbreviated.
Specific comments:
1. Introduction: The text says ‘Currently, most countries have established age 50 as the threshold
for initiating colonoscopy screening2.’ – this is not accurate regarding the age and the modality.
Very few countries use colonoscopy as the main screening tool and I’m not sure that the majority
start at aged 50.
2. Introduction: The text says ‘Additionally, some scholars have suggested that the promotion of
colonoscopy screening in individuals under 50 may lead to an increase in EOCRC incidence due
to earlier detection15’ – which countries are promoting colonoscopy screening in those younger
than 50? This needs to be clearly stated rather than just a reference given.
3. Methods: The text says ‘This study analyzed risk factors with demonstrated causal
relationships with EOCRC, including dietary (low intake of milk, calcium, and fiber, high intake
of red and processed meats), behavioural (alcohol consumption, smoking, and low physical
activity), and metabolic factors (high body mass index and high fasting plasma glucose’ – I don’t
think there is evidence for all of these variables being causally associated with EOCRC?
4. Methods: The text says ‘All methods adhered to relevant guidelines and regulations.’ It is
unclear what the authors are referring to here – should be more specific.
5. Methods: need to be more clear on how the modifiable risk factors were selected.
6. Table S12 – unclear how this table is ordered?
7. Table S12 – unclear what ‘epidemiological changes’ means?
8. Results, Section 3.5: be clear that the statistics in this section refer to 2021 rather than 1990.
9. Results, diet and lifestyle factors: it would help to have a clear explanation of how values for
these variables are determined on a country-wide basis.
10. Discussion: The text says ‘For young individuals, using risk scores to identify high-risk
populations could reduce the burden of colonoscopy,’ – screening does not have to rely on
colonoscopy, the text should reflect this.
11. Discussion: The text says ‘Moreover, the similar risk factors for EOCRC and LOCRC
suggest that unified prevention strategies could be effective’ – I’m not sure this is an evidence-
based statement. There is insufficient data on the aetiology of EOCRC.
12. Discussion: lacks information on why certain countries have the highest or lowest statistic.
Please add some discussion on this.
assistant