Reviewer ’s report  
 
Title: Variables affecting penetrance of gastric and duodenal phenotype in familial adenomatous 
polyposis patients  
 
Version: 0 Date: 03 Apr 2018  
 
Reviewer: Traci Testerman  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload  as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to the authors.  
 
Summary  
Patients with familial adenomatous polyposis (FAP) are at extremely high risk of colon cancer 
and at elevated risk of duodenal cancer.  Depending on the location of mutations within the APC 
gene, patients may have classic or attenuated FAP.  While colonoscopy is done routinely t o 
assess polyps and screen for cancer, it isn't clear whether the frequency of gastric endoscopy 
should be altered based on mutation location or other factors. The authors found that duodenal 
polyp characteristics varied according to genotype and gastric p olyp counts were related to age at 
endoscopy, but significance was lost when smokers or NSAID users were excluded.  Colectomy 
age is not a useful predictor of gastric/duodenal polyps.  The authors conclude that current 
guidelines are adequate and that endo scopy screening frequency should not be changed based on 
genotype.  
 
Major comments  
1. There should be more information on the modified Spigelman classification and its 
applicability in this situation.  The cited manuscript refers only to colonic polyps, n ot gastric 
or duodenal polyps, and did not look specifically at FAP patients.  Is there evidence that the 
assumptions are valid for gastric polyps in FAP patients?  
 
2. How many polyps were evaluated histologically?  It would be useful to discuss these resu lts 
separately from those in which staging was assumed based on polyp size.  
 
3. The figure legend for figure 2 does not differentiate between panels A and B.  
 
Minor comments  
1. The results and conclusions could be stated more clearly, perhaps in summary sent ences.  
 
2. The symbols in figure 1 need to be slightly larger  
 
3. Is it possible that Helicobacter infection could modify the risk of gastric polyp progression?  
Perhaps this should be mentioned.  
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.  
 
I recommend additional statistical review  
 
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 t hat 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, e ither 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 rel ating 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 compet ing 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 revie w policy of the journal  
Reviewer ’s report  
 
Title: Variables affecting penetrance of gastric and duodenal phenotype in familial adenomatous 
polyposis patients  
 
Version: 0 Date: 03 Apr 2018  
 
Reviewer: Traci Testerman  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload  as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to the authors.  
 
Summary  
Patients with familial adenomatous polyposis (FAP) are at extremely high risk of colon cancer 
and at elevated risk of duodenal cancer.  Depending on the location of mutations within the APC 
gene, patients may have classic or attenuated FAP.  While colonoscopy is done routinely t o 
assess polyps and screen for cancer, it isn't clear whether the frequency of gastric endoscopy 
should be altered based on mutation location or other factors. The authors found that duodenal 
polyp characteristics varied according to genotype and gastric p olyp counts were related to age at 
endoscopy, but significance was lost when smokers or NSAID users were excluded.  Colectomy 
age is not a useful predictor of gastric/duodenal polyps.  The authors conclude that current 
guidelines are adequate and that endo scopy screening frequency should not be changed based on 
genotype.  
 
Major comments  
1. There should be more information on the modified Spigelman classification and its 
applicability in this situation.  The cited manuscript refers only to colonic polyps, n ot gastric 
or duodenal polyps, and did not look specifically at FAP patients.  Is there evidence that the 
assumptions are valid for gastric polyps in FAP patients?  
 
2. How many polyps were evaluated histologically?  It would be useful to discuss these resu lts 
separately from those in which staging was assumed based on polyp size.  
 
3. The figure legend for figure 2 does not differentiate between panels A and B.  
 
Minor comments  
1. The results and conclusions could be stated more clearly, perhaps in summary sent ences.  
 
2. The symbols in figure 1 need to be slightly larger  
 
3. Is it possible that Helicobacter infection could modify the risk of gastric polyp progression?  
Perhaps this should be mentioned.  
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.  
 
I recommend additional statistical review  
 
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 t hat 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, e ither 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 rel ating 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 compet ing 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 revie w policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Variables affecting penetrance of gastric and duodenal phenotype in familial adenomatous 
polyposis patients  
 
Version: 0 Date: 03 Apr 2018  
 
Reviewer: Traci Testerman  
 
Reviewer's report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload  as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
Please overwrite this text when adding your comments to the authors.  
 
Summary  
Patients with familial adenomatous polyposis (FAP) are at extremely high risk of colon cancer 
and at elevated risk of duodenal cancer.  Depending on the location of mutations within the APC 
gene, patients may have classic or attenuated FAP.  While colonoscopy is done routinely t o 
assess polyps and screen for cancer, it isn't clear whether the frequency of gastric endoscopy 
should be altered based on mutation location or other factors. The authors found that duodenal 
polyp characteristics varied according to genotype and gastric p olyp counts were related to age at 
endoscopy, but significance was lost when smokers or NSAID users were excluded.  Colectomy 
age is not a useful predictor of gastric/duodenal polyps.  The authors conclude that current 
guidelines are adequate and that endo scopy screening frequency should not be changed based on 
genotype.  
 
Major comments  
1. There should be more information on the modified Spigelman classification and its 
applicability in this situation.  The cited manuscript refers only to colonic polyps, n ot gastric 
or duodenal polyps, and did not look specifically at FAP patients.  Is there evidence that the 
assumptions are valid for gastric polyps in FAP patients?  
 
2. How many polyps were evaluated histologically?  It would be useful to discuss these resu lts 
separately from those in which staging was assumed based on polyp size.  
 
3. The figure legend for figure 2 does not differentiate between panels A and B.  
 
Minor comments  
1. The results and conclusions could be stated more clearly, perhaps in summary sent ences.  
 
2. The symbols in figure 1 need to be slightly larger  
 
3. Is it possible that Helicobacter infection could modify the risk of gastric polyp progression?  
Perhaps this should be mentioned.  
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.  
 
I recommend additional statistical review  
 
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 t hat 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, e ither 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 rel ating 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 compet ing 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 revie w policy of the journal  
assistant