Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 0 Date: 03 Mar 2025
Reviewer's report:
In this manuscript, the authors analyzed global trends (1990–2019) in early-onset
gastrointestinal cancers using GBD data, revealing increased absolute cases but declining age-
standardized rates, with persistent regional disparities and rising colorectal/pancreatic cancer
incidence,which is innovative. However, here are some points to be addressed:
Major points
1. The study heavily relies on GBD 2019 modeled estimates, which may introduce biases to the
results. The authors should explicitly discuss how missing data or regional disparities in data
quality might affect the validity of trends in ASIR/ASDR.
2. The discussion lacks a mechanistic explanation for their differential impacts across regions.
For example, dietary factors are mentioned briefly but not contextualized with regional dietary
habits. A deeper analysis linking risk factors to geographic contexts is needed.
3. The discussion focuses on behavioral and environmental risks but ignores potential genetic
drivers, which are critical in early-onset cancers. The authors should acknowledge this gap and
suggest genetic susceptibility as a confounder or future research direction.
Minor points
1. Recent studies on EO-GI cancers are missing. The authors can update references to reflect
emerging hypotheses beyond traditional risk factors.
2. Some of the sentences in the manuscript are not expressed very accurately, and the grammar
and wording of the article can be improved. The authors can further polish the language.
Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 0 Date: 03 Mar 2025
Reviewer's report:
In this manuscript, the authors analyzed global trends (1990–2019) in early-onset
gastrointestinal cancers using GBD data, revealing increased absolute cases but declining age-
standardized rates, with persistent regional disparities and rising colorectal/pancreatic cancer
incidence,which is innovative. However, here are some points to be addressed:
Major points
1. The study heavily relies on GBD 2019 modeled estimates, which may introduce biases to the
results. The authors should explicitly discuss how missing data or regional disparities in data
quality might affect the validity of trends in ASIR/ASDR.
2. The discussion lacks a mechanistic explanation for their differential impacts across regions.
For example, dietary factors are mentioned briefly but not contextualized with regional dietary
habits. A deeper analysis linking risk factors to geographic contexts is needed.
3. The discussion focuses on behavioral and environmental risks but ignores potential genetic
drivers, which are critical in early-onset cancers. The authors should acknowledge this gap and
suggest genetic susceptibility as a confounder or future research direction.
Minor points
1. Recent studies on EO-GI cancers are missing. The authors can update references to reflect
emerging hypotheses beyond traditional risk factors.
2. Some of the sentences in the manuscript are not expressed very accurately, and the grammar
and wording of the article can be improved. The authors can further polish the language.
Please review this paper.
user
Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 0 Date: 03 Mar 2025
Reviewer's report:
In this manuscript, the authors analyzed global trends (1990–2019) in early-onset
gastrointestinal cancers using GBD data, revealing increased absolute cases but declining age-
standardized rates, with persistent regional disparities and rising colorectal/pancreatic cancer
incidence,which is innovative. However, here are some points to be addressed:
Major points
1. The study heavily relies on GBD 2019 modeled estimates, which may introduce biases to the
results. The authors should explicitly discuss how missing data or regional disparities in data
quality might affect the validity of trends in ASIR/ASDR.
2. The discussion lacks a mechanistic explanation for their differential impacts across regions.
For example, dietary factors are mentioned briefly but not contextualized with regional dietary
habits. A deeper analysis linking risk factors to geographic contexts is needed.
3. The discussion focuses on behavioral and environmental risks but ignores potential genetic
drivers, which are critical in early-onset cancers. The authors should acknowledge this gap and
suggest genetic susceptibility as a confounder or future research direction.
Minor points
1. Recent studies on EO-GI cancers are missing. The authors can update references to reflect
emerging hypotheses beyond traditional risk factors.
2. Some of the sentences in the manuscript are not expressed very accurately, and the grammar
and wording of the article can be improved. The authors can further polish the language.
assistant