Reviewer’s report
Title: The diffuse-type gastric cancer epidemiology enigma
Version: 1 Date: 04 Feb 2020
Reviewer: Petra Hudler
Reviewer's report:
The authors of the article entitled "The diffuse-type gastric cancer epidemiology enigma" attempted to
point out differences in clinical, epidemiological and molecular characteristics between two gastric
adenocarcinoma subtypes, namely, intestinal and diffuse types.  Although this is a very interesting and
relevant topic, the manuscript does not present all the relevant data and is therefore not yet appropriate
for publication. 
General Comments: 
There are some relevant issues that need to be addressed: 1) The authors opted to keep the scope of the
review broad by discussing several aspects related to the pathology of gastric cancer, epidemiology and
so on. However, in several sections, there are missing important data and information, for example, in
some countries, the diffuse type also showed declining incidence, the article does not mention that the
hypothesis that Helicobacter pylori eradication would prevent gastric cancer remains controversial as
some studies indicated that HP eradication did not reduce the risk for developing gastric cancer, next,
the hypothesis that some studies showed a similar DNA methylation levels in HP-related gastritis and
diffuse type of gastric cancer, indicating that H. pylori could be associated with diffuse type of gastric
cancer is also not mentioned, ... With such a complex topic there is a need to thoroughly analyze
specific studies so that interpretations can be delivered in the review clearly and concisely. 2) It is not
clear from general descriptions of data in section Molecular classification and Genetic predisposition,
whereas true molecular distinctions exist between intestinal and diffuse type. The data in those two
sections is also limited and does not represent a vast information on this topic in different experimental
settings and in different populations. 3) The reference list is outdated, in last decade there were several
new complex studies  performed on this topic; the authors should consider including them in the
manuscript.
Minor Comments: 
Introduction, lines 29 - 33; the authors claimed that the intestinal type has been more studied and that
findings have been extrapolated, could the authors provide evidence regarding this claim? 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an additional
statistical review?
If  an  additional  statistical  review  is  recommended,  please  specify  what  aspects  require  further
assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of this
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If
your reply is yes to any, please give details below.
I declare that I have no competing interests.
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for publication, my named report including any 
attachments I upload will be posted on the website along with the authors' responses. I agree for my 
report to be made available under an Open Access Creative Commons CC-BY license 
(http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments which I do not wish to 
be included in my named report can be included as confidential comments to the editors, which will not
be published.
I agree to the open peer review policy of the journal
Reviewer’s report
Title: The diffuse-type gastric cancer epidemiology enigma
Version: 1 Date: 04 Feb 2020
Reviewer: Petra Hudler
Reviewer's report:
The authors of the article entitled "The diffuse-type gastric cancer epidemiology enigma" attempted to
point out differences in clinical, epidemiological and molecular characteristics between two gastric
adenocarcinoma subtypes, namely, intestinal and diffuse types.  Although this is a very interesting and
relevant topic, the manuscript does not present all the relevant data and is therefore not yet appropriate
for publication. 
General Comments: 
There are some relevant issues that need to be addressed: 1) The authors opted to keep the scope of the
review broad by discussing several aspects related to the pathology of gastric cancer, epidemiology and
so on. However, in several sections, there are missing important data and information, for example, in
some countries, the diffuse type also showed declining incidence, the article does not mention that the
hypothesis that Helicobacter pylori eradication would prevent gastric cancer remains controversial as
some studies indicated that HP eradication did not reduce the risk for developing gastric cancer, next,
the hypothesis that some studies showed a similar DNA methylation levels in HP-related gastritis and
diffuse type of gastric cancer, indicating that H. pylori could be associated with diffuse type of gastric
cancer is also not mentioned, ... With such a complex topic there is a need to thoroughly analyze
specific studies so that interpretations can be delivered in the review clearly and concisely. 2) It is not
clear from general descriptions of data in section Molecular classification and Genetic predisposition,
whereas true molecular distinctions exist between intestinal and diffuse type. The data in those two
sections is also limited and does not represent a vast information on this topic in different experimental
settings and in different populations. 3) The reference list is outdated, in last decade there were several
new complex studies  performed on this topic; the authors should consider including them in the
manuscript.
Minor Comments: 
Introduction, lines 29 - 33; the authors claimed that the intestinal type has been more studied and that
findings have been extrapolated, could the authors provide evidence regarding this claim? 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an additional
statistical review?
If  an  additional  statistical  review  is  recommended,  please  specify  what  aspects  require  further
assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of this
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If
your reply is yes to any, please give details below.
I declare that I have no competing interests.
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for publication, my named report including any 
attachments I upload will be posted on the website along with the authors' responses. I agree for my 
report to be made available under an Open Access Creative Commons CC-BY license 
(http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments which I do not wish to 
be included in my named report can be included as confidential comments to the editors, which will not
be published.
I agree to the open peer review policy of the journal
Please review this paper.
user
Reviewer’s report
Title: The diffuse-type gastric cancer epidemiology enigma
Version: 1 Date: 04 Feb 2020
Reviewer: Petra Hudler
Reviewer's report:
The authors of the article entitled "The diffuse-type gastric cancer epidemiology enigma" attempted to
point out differences in clinical, epidemiological and molecular characteristics between two gastric
adenocarcinoma subtypes, namely, intestinal and diffuse types.  Although this is a very interesting and
relevant topic, the manuscript does not present all the relevant data and is therefore not yet appropriate
for publication. 
General Comments: 
There are some relevant issues that need to be addressed: 1) The authors opted to keep the scope of the
review broad by discussing several aspects related to the pathology of gastric cancer, epidemiology and
so on. However, in several sections, there are missing important data and information, for example, in
some countries, the diffuse type also showed declining incidence, the article does not mention that the
hypothesis that Helicobacter pylori eradication would prevent gastric cancer remains controversial as
some studies indicated that HP eradication did not reduce the risk for developing gastric cancer, next,
the hypothesis that some studies showed a similar DNA methylation levels in HP-related gastritis and
diffuse type of gastric cancer, indicating that H. pylori could be associated with diffuse type of gastric
cancer is also not mentioned, ... With such a complex topic there is a need to thoroughly analyze
specific studies so that interpretations can be delivered in the review clearly and concisely. 2) It is not
clear from general descriptions of data in section Molecular classification and Genetic predisposition,
whereas true molecular distinctions exist between intestinal and diffuse type. The data in those two
sections is also limited and does not represent a vast information on this topic in different experimental
settings and in different populations. 3) The reference list is outdated, in last decade there were several
new complex studies  performed on this topic; the authors should consider including them in the
manuscript.
Minor Comments: 
Introduction, lines 29 - 33; the authors claimed that the intestinal type has been more studied and that
findings have been extrapolated, could the authors provide evidence regarding this claim? 
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an additional
statistical review?
If  an  additional  statistical  review  is  recommended,  please  specify  what  aspects  require  further
assessment in your comments to the editors.
Not relevant to this manuscript
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of this
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose
financially from the publication of this manuscript, either now or in the future?
3. Do you hold or are you currently applying for any patents relating to the content of the
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds
or has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If
your reply is yes to any, please give details below.
I declare that I have no competing interests.
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for publication, my named report including any 
attachments I upload will be posted on the website along with the authors' responses. I agree for my 
report to be made available under an Open Access Creative Commons CC-BY license 
(http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments which I do not wish to 
be included in my named report can be included as confidential comments to the editors, which will not
be published.
I agree to the open peer review policy of the journal
assistant