Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 0 Date: 06 Mar 2025
Reviewer:  Peter Muscarella
Reviewer's report:
1) Despite advances in prevention, early detection and management, gastrointestinal cancers
continue to have a high incidence in the world and remain a common cause of death.  Of
particular concern is the rising incidence of early onset gastrointestinal (EO-GI) cancers, defined
as those arising in adults who are less than 50 years old.  This has been firmly established for
colorectal cancer,(1) but there is certainly interest in the epidemiology of other gastrointestinal
cancers in young adults.  The focus on early onset cancers is certainly topical and interesting,
but several studies have previously reported similar results using the same database, some of
which are cited in this paper.(2-6)  The study has essentially been performed and published by
other investigators.  The authors should consider preparing a manuscript that is a comprehensive
review of other studies with a re-analysis of the data.
2) The authors conclude that “understanding the specific burden of GI cancers is crucial for
primary prevention in young adults.”  Although this is undoubtedly true, this is not a conclusion
that is directly supported by the findings of the study.  Perhaps they should include this language
in the background or introduction section.
3) Much of the introduction section is unfocused and does not particularly pertain to the study.
Please consider editing the introduction section for brevity.
4) The authors indicate that no consent form was required for collection of the data and we
assume that this study is exempt from review from the IRB.  This should be stated more clearly.
5) Numerical data are presented in a somewhat interesting fashion in several places in the
manuscript (for example “367.4 thousand”).  Please check for conformity to journal style
guidelines.
6) In the discussion, the authors state that “We found that the absolute number of incidences and
death from overall EO-GI cancer increased from 1990 to 2019.  Two sentences later they state
that ”the incidence and mortality of overall EO-GI cancer decreased during this period, reflecting
years of relentless efforts to prevent, detect and treat EO-GI cancers.”  This is confusing and
contradictory.
1.  The Lancet Gastroenterology H. The rise in early-onset colorectal cancer: now a global issue.
Lancet Gastroenterol Hepatol. 2025;10:95.
2.  Guo C, Liu Z, Lin C, Fan H, Zhang X, Wang H, et al. Global epidemiology of early-onset
liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019. J Glob Health.
2023;13:04167.
3.  Pan H, Zhao Z, Deng Y, Zheng Z, Huang Y, Huang S, et al. The global, regional, and national
early-onset colorectal cancer burden and trends from 1990 to 2019: results from the Global
Burden of Disease Study 2019. BMC Public Health. 2022;22:1896.
4.  Danpanichkul P, Ng CH, Tan DJH, Muthiah MD, Kongarin S, Srisurapanont K, et al. The
Global Burden of Early-Onset Biliary Tract Cancer: Insight From the Global Burden of Disease
Study 2019. J Clin Exp Hepatol. 2024;14:101320.
5.  Danpanichkul P, Auttapracha T, Kongarin S, Ponvilawan B, Simadibrata DM, Duangsonk K,
et al. Global epidemiology of early-onset upper gastrointestinal cancer: trend from the Global
Burden of Disease Study 2019. J Gastroenterol Hepatol. 2024;39:1856-68.
6.  Zhao J, Xu L, Sun J, Song M, Wang L, Yuan S, et al. Global trends in incidence, death,
burden and risk factors of early-onset cancer from 1990 to 2019. BMJ Oncol. 2023;2:e000049.
Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 0 Date: 06 Mar 2025
Reviewer:  Peter Muscarella
Reviewer's report:
1) Despite advances in prevention, early detection and management, gastrointestinal cancers
continue to have a high incidence in the world and remain a common cause of death.  Of
particular concern is the rising incidence of early onset gastrointestinal (EO-GI) cancers, defined
as those arising in adults who are less than 50 years old.  This has been firmly established for
colorectal cancer,(1) but there is certainly interest in the epidemiology of other gastrointestinal
cancers in young adults.  The focus on early onset cancers is certainly topical and interesting,
but several studies have previously reported similar results using the same database, some of
which are cited in this paper.(2-6)  The study has essentially been performed and published by
other investigators.  The authors should consider preparing a manuscript that is a comprehensive
review of other studies with a re-analysis of the data.
2) The authors conclude that “understanding the specific burden of GI cancers is crucial for
primary prevention in young adults.”  Although this is undoubtedly true, this is not a conclusion
that is directly supported by the findings of the study.  Perhaps they should include this language
in the background or introduction section.
3) Much of the introduction section is unfocused and does not particularly pertain to the study.
Please consider editing the introduction section for brevity.
4) The authors indicate that no consent form was required for collection of the data and we
assume that this study is exempt from review from the IRB.  This should be stated more clearly.
5) Numerical data are presented in a somewhat interesting fashion in several places in the
manuscript (for example “367.4 thousand”).  Please check for conformity to journal style
guidelines.
6) In the discussion, the authors state that “We found that the absolute number of incidences and
death from overall EO-GI cancer increased from 1990 to 2019.  Two sentences later they state
that ”the incidence and mortality of overall EO-GI cancer decreased during this period, reflecting
years of relentless efforts to prevent, detect and treat EO-GI cancers.”  This is confusing and
contradictory.
1.  The Lancet Gastroenterology H. The rise in early-onset colorectal cancer: now a global issue.
Lancet Gastroenterol Hepatol. 2025;10:95.
2.  Guo C, Liu Z, Lin C, Fan H, Zhang X, Wang H, et al. Global epidemiology of early-onset
liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019. J Glob Health.
2023;13:04167.
3.  Pan H, Zhao Z, Deng Y, Zheng Z, Huang Y, Huang S, et al. The global, regional, and national
early-onset colorectal cancer burden and trends from 1990 to 2019: results from the Global
Burden of Disease Study 2019. BMC Public Health. 2022;22:1896.
4.  Danpanichkul P, Ng CH, Tan DJH, Muthiah MD, Kongarin S, Srisurapanont K, et al. The
Global Burden of Early-Onset Biliary Tract Cancer: Insight From the Global Burden of Disease
Study 2019. J Clin Exp Hepatol. 2024;14:101320.
5.  Danpanichkul P, Auttapracha T, Kongarin S, Ponvilawan B, Simadibrata DM, Duangsonk K,
et al. Global epidemiology of early-onset upper gastrointestinal cancer: trend from the Global
Burden of Disease Study 2019. J Gastroenterol Hepatol. 2024;39:1856-68.
6.  Zhao J, Xu L, Sun J, Song M, Wang L, Yuan S, et al. Global trends in incidence, death,
burden and risk factors of early-onset cancer from 1990 to 2019. BMJ Oncol. 2023;2:e000049.
Please review this paper.
user
Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 0 Date: 06 Mar 2025
Reviewer:  Peter Muscarella
Reviewer's report:
1) Despite advances in prevention, early detection and management, gastrointestinal cancers
continue to have a high incidence in the world and remain a common cause of death.  Of
particular concern is the rising incidence of early onset gastrointestinal (EO-GI) cancers, defined
as those arising in adults who are less than 50 years old.  This has been firmly established for
colorectal cancer,(1) but there is certainly interest in the epidemiology of other gastrointestinal
cancers in young adults.  The focus on early onset cancers is certainly topical and interesting,
but several studies have previously reported similar results using the same database, some of
which are cited in this paper.(2-6)  The study has essentially been performed and published by
other investigators.  The authors should consider preparing a manuscript that is a comprehensive
review of other studies with a re-analysis of the data.
2) The authors conclude that “understanding the specific burden of GI cancers is crucial for
primary prevention in young adults.”  Although this is undoubtedly true, this is not a conclusion
that is directly supported by the findings of the study.  Perhaps they should include this language
in the background or introduction section.
3) Much of the introduction section is unfocused and does not particularly pertain to the study.
Please consider editing the introduction section for brevity.
4) The authors indicate that no consent form was required for collection of the data and we
assume that this study is exempt from review from the IRB.  This should be stated more clearly.
5) Numerical data are presented in a somewhat interesting fashion in several places in the
manuscript (for example “367.4 thousand”).  Please check for conformity to journal style
guidelines.
6) In the discussion, the authors state that “We found that the absolute number of incidences and
death from overall EO-GI cancer increased from 1990 to 2019.  Two sentences later they state
that ”the incidence and mortality of overall EO-GI cancer decreased during this period, reflecting
years of relentless efforts to prevent, detect and treat EO-GI cancers.”  This is confusing and
contradictory.
1.  The Lancet Gastroenterology H. The rise in early-onset colorectal cancer: now a global issue.
Lancet Gastroenterol Hepatol. 2025;10:95.
2.  Guo C, Liu Z, Lin C, Fan H, Zhang X, Wang H, et al. Global epidemiology of early-onset
liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019. J Glob Health.
2023;13:04167.
3.  Pan H, Zhao Z, Deng Y, Zheng Z, Huang Y, Huang S, et al. The global, regional, and national
early-onset colorectal cancer burden and trends from 1990 to 2019: results from the Global
Burden of Disease Study 2019. BMC Public Health. 2022;22:1896.
4.  Danpanichkul P, Ng CH, Tan DJH, Muthiah MD, Kongarin S, Srisurapanont K, et al. The
Global Burden of Early-Onset Biliary Tract Cancer: Insight From the Global Burden of Disease
Study 2019. J Clin Exp Hepatol. 2024;14:101320.
5.  Danpanichkul P, Auttapracha T, Kongarin S, Ponvilawan B, Simadibrata DM, Duangsonk K,
et al. Global epidemiology of early-onset upper gastrointestinal cancer: trend from the Global
Burden of Disease Study 2019. J Gastroenterol Hepatol. 2024;39:1856-68.
6.  Zhao J, Xu L, Sun J, Song M, Wang L, Yuan S, et al. Global trends in incidence, death,
burden and risk factors of early-onset cancer from 1990 to 2019. BMJ Oncol. 2023;2:e000049.
assistant