The Rise of Gastrointestinal Cancers as a Global Phenomenon: Unhealthy Behavior or Progress?
Round 1
Reviewer 1 Report
The study topic is important and in line with the current epidemiological trends.
Please consider the following changes:
1. I really appreciate the Author's aim to provide something original, however in the case of scientific papers, citation of the literature (even Shakespeare) seems to be inappropriate. I suggest removing lines 31-39 to maintain the scientific standards of this publication.
2. Please provide more epidemiological data on gastrointestinal cancers. 2-3 paragraphs on global prevalence, trends, and regional differences will be sufficient and will strengthen the rationale for this study. The detailed epidemiology is described in section 2, but just some high numbers in the Introduction will be interesting.
3. Please try to revise lines 68-72 to clearly define the study aim
4. I really encourage the Authors to provide a short paragraph on the methodology of this review. Datasets that were analyzed. Scoping review? Narrative review? A short methodological note will strengthen the scientific soundness of this manuscript.
5. Please prove a new section "Future perspective and research needs". This will be an additional value of this manuscript to identify future public health challenges resulting from gastrointestinal cancers as well as to identify future research needs. Practical implications of this study may be also mentioned.
6. Please add 2-3 sentences on the limitations of this review
Author Response
Reviewer#1
The study topic is important and in line with the current epidemiological trends.
Please consider the following changes:
- I really appreciate the Author's aim to provide something original, however in the case of scientific papers, citation of the literature (even Shakespeare) seems to be inappropriate. I suggest removing lines 31-39 to maintain the scientific standards of this publication.
R: We understand this reviewer’s point of view, and we followed his/her suggestion, removing the part mentioned.
- Please provide more epidemiological data on gastrointestinal cancers. 2-3 paragraphs on global prevalence, trends, and regional differences will be sufficient and will strengthen the rationale for this study. The detailed epidemiology is described in section 2, but just some high numbers in the Introduction will be interesting.
R: We appreciate this reviewer’s observation, and we added more information on the epidemiology of GI cancers in the Introduction section. We included some new references in the section: Bray et al, 2018 (new reference #3); Morgan et al, 2022 (new reference #4); Morgan et al, 2022 (new reference #5); Cardoso et al, 2022 (new reference #7); Vuik et al, 2019 (new reference #9); Li, J. 2022. (new reference #10); Islami et al, 2018 (new reference #11); Song et al, 2016 (new reference #12); Arnold et al, 2015 (new reference #13); Arnold et al, 2017 (new reference #15).
- Please try to revise lines 68-72 to clearly define the study aim
R: We understand this reviewer’s point of view, and we have followed his/her suggestion. The aim of this review was to integrate the knowledge regarding the recent rise of GI cancers generated in different fields, through distinct methodologies, analyzing the disease at the individual and the population level, in a more complex and holistic framework (penultimate paragraph of the Introduction).
- I really encourage the Authors to provide a short paragraph on the methodology of this review. Datasets that were analyzed. Scoping review? Narrative review? A short methodological note will strengthen the scientific soundness of this manuscript.
R: We understand this reviewer’s concern, and we followed his/her suggestion, including details of the methodological approach used in the manuscript, in the last part of the Introduction section. In fact, we utilized a predominant scoping approach to address the question of the rise of gastrointestinal cancers as a global phenomenon and the potential role of unhealthy lifestyles. We proposed a new approach to studying gastrointestinal (GI) cancers, discussing the epidemiological aspects, together with the genetic background, epigenetic modifications, gut dysbiosis, and cellular and molecular mechanisms shared by most GI cancers. Furthermore, the impact of unhealthy behaviors, diet, nutrition, and physical activity on developing GI cancers is explored in the context of the progressive globalization of socioeconomic and environmental structures. For this purpose, we performed several searches in PubMed Medline, preferentially focused on GI cancers within the last 20 years, ranging from large database epidemiological analyses to genetic and molecular studies, including concepts of lifestyle, behavior, societal determinants, and syndemic (last paragraph of the Introduction).
- Please prove a new section "Future perspective and research needs". This will be an additional value of this manuscript to identify future public health challenges resulting from gastrointestinal cancers as well as to identify future research needs. Practical implications of this study may be also mentioned.
R: We appreciate this reviewer’s comment, and we followed his/her suggestion, creating a new section #6, just before “Conclusion”. The new section reads “Study limitations and future perspectives”, including two distinct subsections (“Limitations of the current study”, and “Practical implications and research needs”). Part of the previous “Conclusion” was moved to incorporate the “Practical implications and research needs”, in the last paragraph of the subsection. Because of the additional text, we included 6 new references (#201-206).
- Please add 2-3 sentences on the limitations of this review
R: We agree with this reviewer's suggestion, and we included some sentences regarding the limitations of this review, also in the new section (# 6, subsection 6.1 “Limitations of the current study”).
Reviewer 2 Report
I would like to congratulate the authors for the excellent work. It summarises nicely the interplay between the different determinants that contribute to the rise of GI malignancies. An epidemiological shift to younger ages is also noticeable something the authors could further elucidate.
Minor editing:
- CRC is 3rd most common cancer in women (line 118)
- BMI might need to be changed to Increased BMD (181)
- Critical appraisal of other reviews or metanalyses is missing in the text.
Major editing
- I would welcome a short paragraph about recommendations on interventions that could address the phenomenon and health care initiatives, at global level (e.g. WHO initiatives) that could mitigate the risk of rising GI cancer incidence.
- Authors should comment on the rising incidence of early onset GI cancers in the broader context of the rise of GI cancers.
Author Response
Reviewer#2
I would like to congratulate the authors for the excellent work. It summarises nicely the interplay between the different determinants that contribute to the rise of GI malignancies. An epidemiological shift to younger ages is also noticeable something the authors could further elucidate.
R: We thank this reviewer for supporting our work, and appreciate all comments that greatly improved this manuscript.
Minor editing:
- CRC is 3rd most common cancer in women (line 118)
R: We apologize for the mistake, and thank this reviewer for giving us the opportunity of correcting the text.
- BMI might need to be changed to Increased BMD (181)
R: We understand this reviewer’s point of view, and we added BMD to the sentence. But we kept BMI because references 43 and 44 specifically mention BMI.
- Critical appraisal of other reviews or metanalyses is missing in the text.
R: In this manuscript, we ran through several papers in the literature involving GI cancers, including some reviews and metanalyses. Although a specific systematic evaluation of such papers was beyond the scope of this manuscript, we, indirectly, provided a critical appraisal when we selected the literature presented here and identified the large knowledge gaps in the study of GI cancers. Therefore, we believe one of the most important messages in this manuscript is actually the critical view of the limited range and depth of most investigations, basically failing to perform an integrative approach to the multifactorial nature of GI cancers, and also not appropriately analyzing the vast existing literature on the subject.
Major editing
- I would welcome a short paragraph about recommendations on interventions that could address the phenomenon and health care initiatives, at global level (e.g. WHO initiatives) that could mitigate the risk of rising GI cancer incidence.
R: We agree with this comment, and followed this reviewer’s suggestion, including an entirely new section (#6), containing the limitations of our study, potential practical applications, and recommendations.
- Authors should comment on the rising incidence of early onset GI cancers in the broader context of the rise of GI cancers.
R: We agree with this reviewer’s concern, and we included additional references and text on the subject, in the Introduction section (new references #7, 8, and 9). We also included a recent study on muti-omics identifying signatures of early-life environmental exposures (reference #205), which may serve to guide future research projects investigating potential biological imprints of the early-life exposome.
R: We greatly thank both reviewers for supporting our work and for reading in detail all aspects of our study. Their comments allowed us to significantly improve the manuscript.
